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PubMed1991

The AGA1 product is involved in cell surface attachment of the Saccharomyces cerevisiae cell adhesion glycoprotein a-agglutinin.

Saccharomyces cerevisiae a and alpha cells express the complementary cell surface glycoproteins a-agglutinin and alpha-agglutinin, respectively, which interact with one another to promote cellular aggregation during mating. Treatment of S. cerevisiae a cells with reducing agents releases the binding subunit of a-agglutinin, which has been purified and characterized; little biochemical information on the overall structure of a-agglutinin is available. To characterise a-agglutinin structure and function, we have used a genetic approach to clone an a-agglutinin structural gene (AGAI). Mutants with a-specific agglutination defects were isolated, the majority of which fell into a single complementation group, called aga1. The aga1 mutants showed wild-type pheromone production and response, efficient mating on solid medium, and a mating defect in liquid medium; these phenotypes are characteristic of agglutinin mutants. The AGA1 gene was cloned by complementation; the gene sequence indicated that it could encode a protein of 725 amino acids with high serine and threonine content, a putative N-terminal signal sequence, and a C-terminal hydrophobic sequence similar to signals for the attachment to glycosyl phosphatidylinositol anchors. Active a-agglutinin binding subunit is secreted by aga1 mutants, indicating that AGA1 is involved in cells surface attachment of a-agglutinin. This result suggests that AGA1 encodes a protein with functional similarity to the core subunits of a-agglutinin analogs from other budding yeasts. Unexpectedly, the AGA1 transcript was expressed and induced by pheromone in both a and alpha cells, suggesting that the a-specific expression of active a-agglutinin results only from a-specific regulation of the a-agglutinin binding subunit.

Agglutination↗
PubMed1986

Calcium-dependent salivary agglutinin with reactivity to various oral bacterial species.

Human parotid agglutinins from three individuals were isolated by adsorption to and desorption from strains of Streptococcus mutans belonging to serotypes a, b, c, d, and e and strains of Lactobacillus casei, Actinomyces viscosus, and Streptococcus sanguis. The desorption was achieved by suspending centrifuged saliva-coated microorganisms in 10 mM phosphate buffer (pH 6.8) containing 0.154 M sodium chloride. After another centrifugation, agglutinin activity was recovered in the supernatants. The L. casei strain was not agglutinated by any of the agglutinin extracts or by saliva, but all the other strains were agglutinated to a variable extent. However, all strains, including the nonagglutinating L. casei strain, adsorbed and desorbed agglutinins active for other strains. The agglutinin extracts from S. mutans serotype c, S. sanguis, and A. viscosus were purified and characterized by electrophoretic and immunological techniques. The purified preparations were positively stained for protein and carbohydrate, and the molecular weights were estimated to be 440,000. All agglutinin extracts needed calcium in the range of 0.1 to 0.5 mM to be active, and for a single strain, all agglutinins gave the same degree of agglutination, indicating that the isolated agglutinins may be of the same molecular species, a hypothesis that was also confirmed by the preliminary characterization of the purified agglutinins. This type of agglutinin, which seems to exert its activity among various bacterial species, could be important in mediating bacterial coaggregation and thus may add to the effect of specific agglutinins in the clearance of bacteria from the human mouth.

Actinomyces↗
PubMed1987

Differentiation and interaction of secretory immunoglobulin A and a calcium-dependent parotid agglutinin for several bacterial strains.

Previous studies have suggested that both secretory immunoglobulin A (sIgA) and various nonimmunoglobulin salivary glycoproteins are capable of agglutinating a variety of bacteria. The present study was designed to compare the nature of the agglutinins for Streptococcus mutans and Salmonella typhimurium in parotid saliva and colostrum. S. mutans was aggregated by saliva and colostrum, whereas S. typhimurium was aggregated only by saliva as detected by a spectrophotometric method. The principal salivary agglutinin for both S. mutans and S. typhimurium was calcium dependent and could be desorbed in phosphate-buffered saline (pH 6.8). In contrast, the colostral agglutinin was calcium independent and not readily desorbed. The agglutinin activities of saliva and colostrum for S. mutans were additive, suggesting independent target sites on the bacterial surface. The agglutinin activity of colostrum was totally associated with sIgA as was suggested by blocking of the agglutinating activity with anti-alpha-chain serum and the absence of blocking with an antibody specific for salivary agglutinin. Interestingly, anti-alpha-chain serum removed all agglutinating activity from saliva, but not from the phosphate-buffered saline-desorbed agglutinin. Dialysis of parotid saliva against 0.1 M disodium EDTA eliminated the agglutinin blocking activity of anti-alpha-chain serum but not that of the antiagglutinin antibody. The ability of anti-alpha-chain serum to block agglutination of the EDTA-dialyzed saliva could be restored by the addition of calcium chloride, suggesting that sIgA and salivary agglutinin are associated through a calcium-mediated interaction. These results indicate that bacterial agglutinating activity of colostrum, as detected spectrophotometrically, is mediated by sIgA, and that of saliva is mainly dependent upon a calcium-dependent nonimmunoglobulin agglutinin. The agglutinating activities of sIgA and parotid agglutinin seem to be additive, and their calcium-dependent association may favor the enhancement of their respective activities.

Agglutination↗
PubMed1990

A rapid cold agglutinin test in Mycoplasma pneumoniae infection.

A definite diagnosis of Mycoplasma pneumoniae infection is currently based on cultural method or complement fixation test which is usually retrospective. A rapid cold agglutinin test was developed to determine its value on the early diagnosis of M. Pneumoniae infection. One hundred and thirty patients with pneumonia aged between 5 and 14 years were studied. Blood specimens from all the patients were collected for rapid cold agglutinin test, cold hemagglutination test, and complement fixation test. Thirty patients showed positive, rapid cold agglutinin test. All the patients with positive rapid cold agglutinin test had higher (greater than or equal to 1:32) cold agglutinin titers which were simultaneously performed. The rapid cold agglutinin test had 100% sensitivity and 97% specificity when a cut-off criterion was set at cold agglutinin titer greater than or equal to 1:64. Twenty-five of the 130 cases were serologically proven to have M. pneumoniae infection using complement fixation test or/and cold agglutinin titer. M. pneumoniae was a major cause (21/28) in cold agglutinin-positive pneumonic patients. The positive predictive value of the rapid cold agglutinin test is 70% (21/30). Only 28% (7/25) of the patients with M. pneumoniae infection were diagnosed at acute stage with serological method. We conclude that the rapid cold agglutinin test is of much value in the early detection of M. pneumoniae infection in office or hospital practice in children with pneumonia.

Adolescent↗
PubMed2003

Anti-nutritional effects of a moderate dose of soybean agglutinin in the rat.

This study was conducted to investigate the effects of a moderate dose of purified soybean agglutinin on performance and nitrogen digestibility in rats as well as to determine its effects on the protein, DNA and RNA content of the small intestine and pancreas. Twenty-four Sprague-Dawley rats were randomly allotted into one of four groups for a 10-day nitrogen balance experiment. The four groups of rats were fed 7 g of a casein-cornstarch based diet or a similar diet supplemented with 0.1, 0.2 or 0.4 mg/g purified soybean agglutinin. All experimental diets were adjusted to an identical nutrient level. Dose of soybean agglutinin had no significant effect on rat performance. Incorporation of soybean agglutinin in the diet reduced apparent protein digestibility and the utilization of dietary protein by increasing nitrogen loss from the faeces and urine. Fresh pancreatic weight increased in rats fed soybean agglutinin at a level of 0.4 mg/g in the diet compared to the control, but the dry pancreatic weight and the protein content of the pancreas did not differ among the four groups. However the DNA and RNA content of the pancreas had a tendency to increase with a higher level of soybean agglutinin. The weight of the jejunum and its protein, DNA and RNA content were not significantly affected by soybean agglutinin, but the dry weight and the RNA of the jejunum tended to increase with higher levels of soybean agglutinin in the diet. In conclusion, purified soybean agglutinin, at moderate levels in the rats diet, had negative effects on digestive function, such as nitrogen digestibility, nitrogen retention and nitrogen balance. As the level of soybean agglutinin increased, the effects became more pronounced. Meanwhile, hypertrophy of the pancreas was observed with higher doses of soybean agglutinin incorporation in the diets.

Animal Feed↗
PubMed2003

Effects of soybean agglutinin on nitrogen metabolism and on characteristics of intestinal tissues and pancreas in rats.

Two experiments were conducted to investigate the effects of increasing concentrations of supplemental purified soybean agglutinin on performance, apparent nitrogen digestibility, plasma insulin and cholecystokinine (CCK) levels in rats as well as on the growth of the small intestine and pancreas. In Experiment 1, a 10-day nitrogen balance trial was conducted with 24 male Sprague-Dawley rats (mean BW 85 g) that were randomly allotted to one of four dietary treatments. Rats in each group were provided daily with 7 g of a casein-cornstarch based diet (control) or a diet supplemented with purified soybean agglutinin at 0.4, 0.6 or 0.8 mg/g. Urine and faeces were collected daily and stored at -20 degrees C until analysis. In Experiment 2, 30 male Sprague-Dawley rats (mean BW 75 g) were divided into five groups for a 20-day growth experiment. Each rat was fed daily 7 g of a casein-cornstarch based diet (control) or a diet supplemented with purified soybean agglutinin at 0.4, 0.8, 1.2 or 2.0 mg/g. All experimental diets were adjusted to contain a similar level of nutrients. Results from the two experiments showed that supplementation of soybean agglutinin below 2.0 mg/g diet had no significant effect on rat performance. However, rats receiving 2.0 mg soybean agglutinin per gram of diet showed a significant reduction in weight gain compared to the control group. Incorporation of soybean agglutinin in the diet reduced apparent nitrogen digestibility and the retention of dietary nitrogen by increasing nitrogen loss from the faeces and urine. In addition, plasma CCK level increased with increasing inclusion of soybean agglutinin in the diet. On the contrary, the plasma insulin level declined as soybean agglutinin level increased. Soybean agglutinin induced a polyamine-dependent hyperplastic and hypertrophic growth of the small intestine and pancreas by increasing the contents of protein, RNA and DNA, though the increase in weight of small intestine was not significant. Furthermore, 1.2 and 2.0 mg soybean agglutinin per gram of diet promoted proliferation of the jejunum mucosa, while the structure of the brush border epithelium of small intestinal had no damaging change and no diarrhoea was observed in any treatment group. Based on these results, supplementation of low doses of soybean agglutinin or soy protein to parenterally-fed animals affected by atrophic small intestine may promote small intestinal growth.

Animals↗
PubMed1999

Thermal stability and mode of oligomerization of the tetrameric peanut agglutinin: a differential scanning calorimetry study.

Peanut agglutinin is a homotetrameric legume lectin. The crystal structure of peanut agglutinin shows that the four subunits associate in an unusual manner, giving rise to open quaternary structure [Banarjee, R., et al. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 227-231]. The thermal unfolding of peanut agglutinin has been characterized by differential scanning calorimetry and gel filtration to elucidate its thermal stability and its mode of oligomerization. The unfolding process is reversible and could be described by a three-state model with two transitions occurring at around 331 and 336 K. For the tetramer, the ratio of DeltaHc/DeltaHv for the first transition is close to 4 and for the second transition is close to 0.25, suggesting that 4 and 0.25 cooperative unit(s) of the tetramer are involved in the first and second transitions, respectively. The agreement between the model-independent DeltaHv(S) determined from the values of the temperatures of the peak maximum (Tp1) with the protein concentration with the values of DeltaHv obtained from the fit of the data to the transition confirms that the first peak is associated with the dissociation of peanut agglutinin tetramers (A4) to "folded" monomers (4A), whereas the second peak describes the unfolding (4U) of these monomers. The overall process for the thermal unfolding of peanut agglutinin could therefore be summarized as A4 <==> 4A <==> 4U. Gel filtration studies confirm this process, as peanut agglutinin elutes as a tetramer up to 50 degrees C, and at and above 56 degrees C (Tm of first transition), it elutes at a position commensurate with that of the folded monomer of peanut agglutinin. The unfolding behavior of peanut agglutinin in the presence of saturating amounts of carbohydrate ligands is similar to that observed for the unligated form. The temperature of maximal stability of the peanut agglutinin tetramer at pH 7.4 is calculated to be around 33 degrees C with a maximal free energy of stabilization of 8.70 kcal/mol. The results demonstrate that unfolding of peanut agglutinin goes through two distinct phases with folded monomer being the intermediate.

Calorimetry, Differential Scanning↗
PubMed2000

A role for Lewis a antigens on salivary agglutinin in binding to Streptococcus mutans.

Streptococcus mutans is a major etiological agent in dental caries. Salivary agglutinin is one of the main salivary components binding to S. mutans. To learn more about the interaction of salivary agglutinin with S. mutans, parotid, submandibular, sublingual and palatal saliva samples were incubated with S. mutans suspension. Both depleted saliva samples and bacterial extracts were analyzed by SDS-PAGE and immunoblotting. Salivary agglutinin was present in all types of glandular saliva and in all cases bound to S. mutans, also to PC337C, a P1 mutant of S. mutans. Agglutinin was separated by SDS-PAGE under reducing and non-reducing conditions and then transferred to nitrocellulose. Non-reduced agglutinin bound S. mutans, but reduced agglutinin did not. Adhesion of S. mutans to agglutinin-coated microplates was inhibited by amine-containing components, 1 M NaCl or KCl and EDTA. Adhesion decreased with decreasing pH with no adhesion below pH 5.0. These data suggest that calcium-dependent electrostatic interactions play a role in binding. By immunoblotting was demonstrated that blood group antigens and Lewis antigens were present on agglutinin. Synthetic blood group antigens and Lewis antigens covalently coupled to polyacrylamide were tested for binding to S. mutans. Only Le(a)(Gal beta 1,3(Fuc alpha 1,4)GlcNAc) bound to S. mutans, whereas the blood group antigens Le(b), Le(x), Le(y), H1, H2, A, B and sialylated Le(a) did not. Lea without galactose (Fuc alpha 1,4GlcNAc) still bound to S. mutans, but Le(a) without fucose (Gal beta 1,3GlcNAc) did not. Binding of agglutinin to S. mutans was not inhibited by Le(a). In conclusion, S. mutans can bind to Le(a) carbohydrate epitopes in which the fucose is an essential residue. Le(a) carbohydrate epitopes are present on salivary agglutinin but play no major role in binding.

Agglutinins↗
PubMed1996

Do cold agglutinins have any impact on the outcome of liver transplantation?

Cold agglutinins, IgM red blood cell autoantibodies, cause cold agglutinin disease with hemolysis and microvascular occlusion. Cold preservation of kidneys during renal transplantation in the presence of cold agglutinins can cause graft malfunction. However, the impact of cold agglutinins on the outcome of liver transplantation is unknown. We measured the pretransplant presence and titer of cold agglutinins in 327 primary liver allograft recipients and analyzed their relationship to outcome after transplant. Thirty-three percent of pretransplant patients had cold agglutinins. Cold agglutinins were more common in patients with viral-related liver diseases (49%) compared with those with nonviral-related liver disease (32%). There was no difference between recipients with and without cold agglutinins in usage of blood products, postoperative day 2 aminotransferase levels, acute rejection at day 7, the development of hepatic artery thrombosis, nonanastomotic biliary strictures, or 4-month allograft survival. In conclusion, cold agglutinins are common in liver transplant patients before surgery, especially those with viral-related liver diseases. However, the presence of cold agglutinins does not impact on outcome after liver transplantation.

Agglutinins↗
PubMed1983

Acetone-treated agglutinin against Yersinia pseudotuberculosis in free-living rats.

Retrospective investigation was done on Yersinia pseudotuberculosis infection in barn rat populations living in an Yersinia endemic area and in zoo rat populations living in a nonendemic area. The OH agglutinins against Y pseudotuberculosis were normally distributed within both populations. Most of the OH agglutinin titers and many O agglutinin titers were reduced by treatment of sera with acetone. Sera with O and OH agglutinin titers were assigned to 2 groups, one with a titer less than 1:8 and the other with a titer of greater than or equal to 1:8. Rats harboring the organism did not possess O or OH agglutinin titers greater than 1:8 in acetone-treated sera. In most nontreated sera, OH agglutinin titers were higher than were the O agglutinin titers. However, in most acetone-treated sera, O agglutinin titers were equivalent to OH agglutinin titers. Differences by region and age were observed in acetone-treated O agglutinin titers of greater than or equal to 1:8 against Y pseudotuberculosis. Therefore, it is recommended that to detect antibody against Y pseudotuberculosis in rats, sera should be treated with acetone before the test and O antigen should be used.

Acetone↗
PubMed1991

Saccharomyces cerevisiae a- and alpha-agglutinin: characterization of their molecular interaction.

An O-glycosylated protein of approximately 18 kDa responsible for mating type specific agglutination has been isolated from Saccharomyces cerevisiae a cells, purified to homogeneity and via peptide sequences the gene was cloned by PCR. An open reading frame codes for a protein of 69 amino acids. A minimum of five serine and five threonine residues of the mature protein are glycosylated. alpha-Agglutinin is a highly N-glycosylated protein of approximately 250 kDa. Both purified agglutinins form a specific 1:1 complex in vitro. Pretreatment of alpha-agglutinin, but not of alpha-agglutinin, with diethylpyrocarbonate (DEPC) prevents formation of the complex; treatment of alpha-agglutinin in the presence of alpha-agglutinin protects the former from DEPC inactivation. By carboxy terminal shortening of the alpha-agglutinin gene and by replacing three of its eight histidyl residues by arginine, the active region of alpha-agglutinin for interaction with alpha-agglutinin has been defined. Neither the N- nor the O-linked saccharides of the two agglutinins seem to be essential for their interaction.

Base Sequence↗
PubMed1998

Evolution of tetrameric lectin Ricinus communis agglutinin from two variant groups of ricin toxin dimers.

Seeds of Ricinus communis contain two types of lectins; the toxin ricin (approximately 60 kDa) and R. communis agglutinin (approximately 120 kDa). The toxin is a heterodimer composed of a toxic A subunit and a lectin B subunit, while R. communis agglutinin is a tetramer, constituted of two ricin-like dimers held together by non-covalent forces. The lactamyl Sepharose affinity-purified ricin consists of two major groups of variants designated ricin II and III [Hegde, R. & Podder, S. K. (1992) Eur. J. Biochem. 204, 155-164]. The purified A subunits of all the variants of ricins and R. communis agglutinin show heterogeneity in the molecular mass as shown for ricin before [Fulton, J. R., Blakey, C. D., Knowles, P. P., Uhr, J. W., Thorpe, P. E. & Vitetta, E. S. (1986) J. Biol. Chem. 261, 5314-5319]. Since the isoelectric points of the R. communis agglutinin variants fall between the isoelectric points of ricin II and III, we investigated the possibility that this lectin is made up of ricin II and III. The isoelectric points of the purified B subunits of R. communis agglutinin matched well with those of ricin II and III on urea-polyacrylamide isoelectric focussing gel. Further, two-dimensional electrophoretic analysis of the ricin constituants of R. communis agglutinin in the presence of 9 M urea, showed two protein bands, differing by nearly pH 2 in their isoelectric points, the more alkaline one corresponding to that of ricin III analyzed under the same conditions, while the other, although a higher molecular mass variant, corresponding well with ricin II in its isoelectric point. Based on these results and those obtained from adenine binding to A chains of both ricin and R. communis agglutinin, we provide a plausible evolutionary relationship between R. communis agglutinin and two groups of ricin variants; ricin II and III. The model predicts that one half of R. communis agglutinin is derived from ricin I and II, and the other half from ricin III. The results presented, contrary to the existing notion, unequivocally show that the two halves of R. communis agglutinin are not identical protein units, but differ both in surface charge and molecular mass.

Ricinus communis↗
PubMed2006

Structure-function analysis and insights into the reduced toxicity of Abrus precatorius agglutinin I in relation to abrin.

Abrin and agglutinin-I from the seeds of Abrus precatorius are type II ribosome-inactivating proteins that inhibit protein synthesis in eukaryotic cells. The two toxins share a high degree of sequence similarity; however, agglutinin-I is weaker in its activity. We compared the kinetics of protein synthesis inhibition by abrin and agglutinin-I in two different cell lines and found that approximately 200-2000-fold higher concentration of agglutinin-I is needed for the same degree of inhibition. Like abrin, agglutinin-I also induced apoptosis in the cells by triggering the intrinsic mitochondrial pathway, although at higher concentrations as compared with abrin. The reason for the decreased toxicity of agglutinin-I became apparent on the analysis of the crystal structure of agglutinin-I obtained by us in comparison with that of the reported structure of abrin. The overall protein folding of agglutinin-I is similar to that of abrin-a with a single disulfide bond holding the toxic A subunit and the lectin-like B-subunit together, constituting a heterodimer. However, there are significant differences in the secondary structural elements, mostly in the A chain. The substitution of Asn-200 in abrin-a with Pro-199 in agglutinin-I seems to be a major cause for the decreased toxicity of agglutinin-I. This perhaps is not a consequence of any kink formation by a proline residue in the helical segment, as reported by others earlier, but due to fewer interactions that proline can possibly have with the bound substrate.

Abrin↗
PubMed1995

Glycosyl phosphatidylinositol-dependent cross-linking of alpha-agglutinin and beta 1,6-glucan in the Saccharomyces cerevisiae cell wall.

The cell adhesion protein alpha-agglutinin is bound to the outer surface of the Saccharomyces cerevisiae cell wall and mediates cell-cell contact in mating. alpha-Agglutinin is modified by addition of a glycosyl phosphatidylinositol (GPI) anchor as it traverses the secretory pathway. The presence of a GPI anchor is essential for cross-linking into the wall, but the fatty acid and inositol components of the anchor are lost before cell wall association (Lu, C.-F., J. Kurjan, and P. N. Lipke, 1994. A pathway for cell wall anchorage of Saccharomyces cerevisiae alpha-agglutinin. Mol. Cell. Biol. 14:4825-4833). Cell wall association of alpha-agglutinin was accompanied by an increase in size and a gain in reactivity to antibodies directed against beta 1,6-glucan. Several kre mutants, which have defects in synthesis of cell wall beta 1,6-glucan, had reduced molecular size of cell wall alpha-agglutinin. These findings demonstrate that the cell wall form of alpha-agglutinin is covalently associated with beta 1,6-glucan. The alpha-agglutinin biosynthetic precursors did not react with antibody to beta 1,6-glucan, and the sizes of these forms were unaffected in kre mutants. A COOH-terminal truncated form of alpha-agglutinin, which is not GPI anchored and is secreted into the medium, did not react with the anti-beta 1,6-glucan. We propose that extracellular cross-linkage to beta 1,6-glucan mediates covalent association of alpha-agglutinin with the cell wall in a manner that is dependent on prior addition of a GPI anchor to alpha-agglutinin.

Antibodies↗
PubMed1994

Isolation and partial purification of mannose-specific agglutinin from brewer's yeast involved in flocculation.

Yeast cell-agglutinating activity, designated agglutinin (possible lectin), was isolated from cell walls of both non-flocculent and flocculent brewer's yeast cells. Agglutinin-mediated aggregation of yeast cells in a manner similar to flocculation with respect to specific mannose-sensitivity, pH-dependence and calcium-dependence. Agglutinating activity was found to be heat-stable and protease-insensitive. Furthermore, addition of agglutinin to flocculent cells strongly stimulated the flocculation ability of the cells, whereas addition to non-flocculent cells rendered these cells weakly flocculent. Agglutinin was found to be released from flocculent cells during the course of a flocculation assay, but not from non-flocculent cells. Presence of mannose during the assay inhibited release of agglutinin. Our results suggest that (i) mannose-specific agglutinin is continuously synthesized during growth of brewer's yeast cells, (ii) agglutinin is present in cell walls of non-flocculent cells but is unable to bind its ligand on other cells, and (iii) the ability of yeast cells to flocculate in a flocculation assay depends, among other factors, on release of agglutinin from the cells. A 10-kDa polypeptide might represent one form of agglutinin.

Agglutinins↗
PubMed1994

Waldenström's macroglobulinemia with an IgM paraprotein that is both a cold agglutinin and a cryoglobulin and has a suppressive effect on progenitor cell growth.

BACKGROUND: A patient with Waldenström's macroglobulinemia was admitted to the hospital with fever, leg pain, and dyspnea. The patient had gas gangrene of the left leg that required above-the-knee amputation. Plasmapheresis was instituted to treat hyperviscosity. STUDY DESIGN AND METHODS: The patient's serum contained an IgM-kappa paraprotein, a cryoglobulin, and a cold agglutinin. The serum was studied. RESULTS: The patient's red cells typed as A1, Rh-positive. The direct antiglobulin test was negative. The serum contained a cold agglutinin with anti-Pr cold agglutinin specificity (titer 4096). Maximal thermal range was 30 degrees C. Following dithiothreitol treatment, the cold agglutinin activity disappeared. The serum IgM concentration in the tested sample was 62.3 g per L. The cold agglutinin titer in the supernatant after removal of the cryoglobulin was 256, and the IgM level was 0.31 g per L. Redissolving the cryoglobulin in a equivalent volume of saline resulted in a cold agglutinin titer of 4096 and an IgM level of 68.4 g per L. These results indicate that the cryoglobulin and the cold agglutinin are the same paraprotein. Serum protein electrophoresis using agarose gel and immunofixation of the serum revealed an IgM-kappa monoclonal band. Progenitor cell assays were performed by adding the patient's serum at final concentrations of 0, 1, 5 and 10 percent (vol/vol) to patient's and normal donor's peripheral blood mononuclear cells. Inhibition of burst-forming units-erythroid and colony-forming units-granulocyte/macrophage by the patient's serum was demonstrated. Appropriate controls and the use of the serum of another patient with Waldenström's macroglobulinemia did not suppress progenitor cell growth. The patient's serum inhibited colony formation in a dose-response fashion. CONCLUSION: Reports of cryoprecipitable cold agglutinins are rare. This case is unusual because the IgM-kappa paraprotein was also a cold agglutinin with anti-Pr specificity and erythroid and granulocyte-macrophage progenitor cell-suppressive properties.

Agglutinins↗
PubMed2004

Restriction in the repertoire of the immunoglobulin light chain subgroup in pathological cold agglutinins with anti-Pr specificity.

BACKGROUND AND OBJECTIVES: In cold agglutinin disease, monoclonal red blood cell autoantibodies, termed cold agglutinins, induce haemolysis in patients exposed to the cold. Commonly, these autoantibodies are directed against the developmentally regulated I/i blood groups. A second blood group system, the Pr system (located on glycophorins), is involved less frequently. Anti-Pr cold agglutinins recognize either alpha 2,3- or alpha 2,6-linked N-acetylneuraminic acid as the immunodominant group. Cold agglutinins of anti-I/i specificity show a remarkable restriction in their genomic repertoire of the immunoglobulin heavy and light-chain immunoglobulin-variable domain (i.e. exclusive use of VH4-34 in heavy chains). For anti-Pr cold agglutinins, preliminary data on the repertoire of the light-chain variable domain indicate a preference for the subgroup Vkappa IV. To elucidate restrictions in the light-chain variable-domain subgroup repertoire of anti-Pr cold agglutinins systematically, and to discuss these results in the context of their anti-Pr(1-3) subclassification and immunodominant sialic acid, light chains in 13 anti-Pr cold agglutinins were investigated. MATERIALS AND METHODS: The anti-Pr light chains were isolated using temperature-dependent absorption/elution techniques. Subsequently, they were subjected to N-terminal Edman degradation, and the light chain Vkappa subgroup was affiliated using the Kabat database. RESULTS: Five of 13 (38%) light chains belonged to Vkappa IV, five of 13 (38%) to Vkappa I and three of 13 (23%) to Vkappa III. Anti-Pr with Vkappa IV subgroup light chains exclusively recognized alpha 2,3-linked N-acetylneuraminic acid. CONCLUSIONS: Including data from the literature, the repertoire of the light-chain variable domain in pathological anti-Pr cold agglutinins exhibits a clear bias towards the use of the single germline gene-derived subgroup, Vkappa IV (eight of 17 or 47%). The association of Vkappa IV subgroup light chain-containing anti-Pr cold agglutinins with binding to alpha 2,3-, but not alpha 2,6-linked N-acetyneuraminic acid raises speculations about a possible role of subgroup-derived determinants in anti-Pr binding.

Adult↗
PubMed1994

Activation of complement by cold agglutinins.

OBJECTIVE: To review recent reports on the interaction of cold agglutinins with the complement system and its relevance to cold agglutinin disease. DATA SOURCES: Review articles and original papers have been selected for this contribution. SELECTION CRITERIA: The report focuses on experimental data available from in vitro studies as well as clinical findings regarding the mechanisms of cold agglutinin-induced complement activation. RESULTS: Despite the observation that only few cold agglutinins (almost exclusively IgM molecules with anti-I specificity) induce in vitro hemolysis of human red blood cells with human serum (homologous system), the vast majority of these autoantibodies are able to initiate the classical pathway sequence with the fixation of C1 and to a lesser degree of C4. The ability of IgM cold agglutinins to activate, in principle, complement is demonstrated by their hemolytic efficiency in the presence of animal serum as a source of heterologous complement. In addition to the thermal amplitude of cold agglutinin binding, a possible interference with membrane regulatory proteins may render certain cold agglutinins hemolytically active in a homologous system. CONCLUSION: Despite a hemolytic inefficiency, cold agglutinin-induced fixation of early complement components up to C3 leads to an accelerated clearance of red cells from the circulation by hepatic sequestration. However, it is not yet clear, to what degree these cells are eliminated by the reticuloendothelial system or whether they return to the circulation. Dependent on the amount of membrane-bound C3 fragments these cells may even be protected against further cold agglutinin-induced complement attack.

Agglutinins↗