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D Roelcke

Publications and source records attributed to D Roelcke.

At least 19 recordsLinked to original sources
PubMed2001

[Cold agglutinins of the IgM class in a patient with monoclonal gammopathy of the IgA class].

HISTORY AND CLINICAL PRESENTATION: A 61-year-old patient was examined in hospital because he had suffered from fatigue and weight loss for several years. History and physical examination showed no symptoms specific for a disease of a particular organ except a goitre. INVESTIGATIONS: Laboratory examination serum showed a decreased haptoglobin, a slightly elevated bilirubin, an acceleration of the blood sedimentation rate and a M-gradient in the protein electrophoresis. The immunofixation electrophoresis revealed a monoclonal gammopathy of the IgA-class. The cold agglutinin titre was clearly elevated (2048 at 4 degrees C), caused by an auto-anti-I of the IgM-class. No signs of an infection or a haematological neoplasm were found. TREATMENT AND COURSE: No specific therapy was given for the compensated haemolytic anaemia and the monoclonal gammopathy. There was no significant change in the course of the disease over 5 years. CONCLUSION: Between the specificity and the immunoglobulin class of cold agglutinins correlations exist that are also of significance for these autoantibodies. As shown by this case, an exact analysis of the specificity and the immunoglobulin class of cold agglutinins should be done in cases with unusual combinations of laboratory results to prevent misleading interpretations.

Agglutinins↗
PubMed2001

Autoimmune hemolytic anemia caused by IgG lambda-monotypic cold agglutinins of anti-Pr specificity after rubella infection.

BACKGROUND: In postinfection cold agglutinin (CA) disease, a relation between CA specificity and the underlying infectious agent has been observed. The induction of anti-I by Mycoplasma pneumoniae and that of anti-i by EBV are well-established examples. CASE REPORT: A 5-year-old boy developed severe hemolytic anemia after serologically ascertained rubella infection. Hemolysis was caused by high-titer CAs, which were analyzed by absorption and elution with sialidase-treated RBCs and hemagglutination-inhibition experiments. RESULTS: After elimination of normal anti-I and anti-T, the predominant CA was found to be an IgG lambda autoantibody with anti-Pr(1) specificity. CONCLUSION: This case seems to be of interest because it is the first report of severe CA-induced hemolysis after rubella infection, it is the first description of an IgG lambda-monotypic CA, and, along with previous case reports (three established and three suspected cases), it indicates a relationship between rubella infection and the CA specificity anti-PR:

Agglutinins↗
PubMed2000

Coexisting Anti-I/i Plus Anti Pr Cold Agglutinins in Individual Sera.

Background: Sera with high-titer cold agglutinins (CAs) of unclear or even of apparently definite specificity may contain mixtures of CAs with different specificities. The combination of anti-I plus anti-Sia-b1 CAs in sera of patients with Mycoplasma pneumoniae infections is well documented. No systematic studies on CA mixtures in sera of patients with other diagnoses are available. Material and Methods: Sera of 322 patients with high-titer CAs were exhaustively absorbed with sialidase-treated red blood cells (RBCs). By absorption, CAs against the sialidase-resistant I/i antigens are removed. If CAs reacting with untreated RBCs are left after absorption, they are directed against the sialidase- and protease-sensitive Pr(1,2,3) antigens or against the sialidase-labile but protease-resistant antigens of the Sia-I/b/Ib complex. If CA mixtures were found, specificities and isotypes of the CAs obtained by cold adsorption and warm elution were determined. Results: Three patients had mixtures of anti-i plus anti-Pr CAs, 2 patients had mixtures of anti-I plus anti-Pr CAs. Conclusion: The occurrence of CAs directed against biochemically different antigens in individual sera proves two autoimmune processes against the same cells (erythrocytes) in the same patient. One explanation for this constellation would be a postinfection cold agglutination in a patient with chronic CA disease. Copyright 2000 S. Karger GmbH, Freiburg

Journal Article↗
PubMed1999

Inverse association between IgG-anti-kappa and antierythrocyte autoantibodies in patients with cold agglutination.

It has been known for a long time that IgG-anti-F(ab')(2) antibodies (Abs) are able to suppress the B-cell response. We showed that natural IgG-anti-F(ab')(2) autoantibodies appear in the serum of patients with cold agglutination. If the anti-F(ab')2 Ab suppresses cold agglutinin (CA)-producing B cells, one would expect an inverse correlation between the titers of these two Abs. Our study confirmed this correlation. Subsequent experiments showed that some anti-F(ab')(2) Abs bind to the hinge region of IgG. It was difficult to explain how this Ab suppresses CA-producing B cells, which are of IgM isotype. Here we show that patients with cold agglutination have an IgG-anti-kappa light chain autoantibody in their serum. This is another member of the anti-F(ab')(2) Ab group. Because the vast majority of CAs are IgM-kappa Abs, the anti-kappa Ab might suppress CA-producing B cells. If this is the case, there should be an inverse association between the titer of anti-kappa Ab and CA. In a group of 302 patients, we found that high titers of the anti-kappa Ab correlate with low titers of CA and vice versa (P =.009). Interestingly, this association is found only in patients whose disease is caused by noninfectious agents, including mainly B-cell proliferations (P =.0058). Our data show that the inverse correlation is not confined to a particular CA autoantibody specificity. The results are discussed in the light of recent findings showing that anti-IgM Abs may either inactivate or kill tumoral B cells by apoptosis.

Anemia, Hemolytic, Autoimmune↗
PubMed1998

Alpha 2,3-specific desialylation of human red cells: effect on the autoantigens of the Pr, Sa and Sia-l1, -b1, -lb1 series.

BACKGROUND AND OBJECTIVES: Pr1,2,3, PrM, Sa and Sia-l1, -b1, -lb1 are sialic acid (NeuNAc)-dependent antigens recognized by human cold agglutinins. Pr and Sa antigens are the O-glycans of glycophorins containing alpha 2,3NeuNAc (to galactose) and/or alpha 2,6NeuNAc (to galactosamine). The antigens of the Sia-l1, -b1, -lb1 complex are gangliosides that may carry alpha 2,3NeuNAc (to galactose) and/or alpha 2,8NeuNAc (to NeuNAc). We studied the NeuNAc groups involved in the antigens. MATERIALS AND METHODS: From 74 sera with cold agglutinins against NeuNAc-dependent antigens, anti-T-free preparations were made and tested against human red cells, treated with an alpha 2,3-specific recombinant sialidase. RESULTS: Most (51/62) Pr antigens use alpha 2,3NeuNAc, some (8/62) use alpha 2,6NeuNAc and a few (3/62) use both sialyl groups as immunodominant components on glycophorins. The immunodominant component of Sa and Sia-l1, -b1, -lb1 determinants was alpha 2,3NeuNAc in all cases. CONCLUSION: The red cell target structures for cold agglutinins against NeuNAc-dependent antigens have been identified. We propose a Pr nomenclature to reflect this. The binding of anti-Pr to gangliosides may be the basis for anti-Pr-induced peripheral neuropathy.

Autoantigens↗
PubMed1998

Serum affinity chromatography for the detection of IgG alloantibodies in a patient with high-titer IgM cold agglutinins.

BACKGROUND AND OBJECTIVES: High-titer cold autoagglutinins (CA) interfere with the detection of alloantibodies against red-blood-cell antigens. The diagnostic procedure is extremely difficult, especially under pressure of time. It was the purpose of the study to find out whether quantitative IgG purification from serum or plasma by affinity chromatography facilitates the detection of IgG alloantibodies in the presence of high-titer IgM CA. MATERIALS AND METHODS: Serum: IgM-chi CA, 0 degrees C titer = 65,000; five anti-IgG reactive alloantibodies. Affinity chromatography: HiTrap protein G 1-ml affinity column (Pharmacia Biotech, Uppsala, Sweden). RESULTS: All IgG alloantibodies were detectable in the eluate after affinity chromatography without interference of IgM CA. CONCLUSION: IgG alloantibodies in the presence of high-titer IgM CA can be easily and rapidly detected under routine conditions by quantitative IgG purification from serum or plasma by affinity chromatography.

Anemia, Hemolytic, Autoimmune↗
PubMed1997

Anti-Sia-lb (anti-Gd) cold agglutinins bind the domain NeuNAc alpha2-3Gal in sialyl Lewis(x), sialyl Lewis(a), and related carbohydrates on nucleated cells and in soluble cancer-associated mucins.

Anti-Sia-lb (formerly anti-Gd) cold agglutinins (CAs) recognize sialylated carbohydrates on both adult and neonate red blood cells (RBCs). RBC CA activity inhibition experiments reported here indicate that the domain NeuNAc alpha2-3Gal, as found in sialyllactose, synthetic sialyl(s) Lewis(Le)(x) and sLe(a), sialyllactosamine, sialyl-fucosyllactose, and nonfucosylated sLe(a), constitutes the minimal epitope for these CAs, implicating that these autoantibodies could be able to bind this domain in sLe(x) and sLe(a) and related carbohydrates expressed on nucleated cells and in soluble cancer-related mucins. The following data obtained with the previously characterized monoclonal IgMk anti-Sia-lb CA, GAS, show that this is the case. GAS epitope expression among leukocytes that lack sLe(a) parallels that of sLe(x) determinant as detected by mouse monoclonal antibodies (MoAbs), especially MoAb KM-93. It is also found on epithelial malignant cells bearing both sLe(x) and sLe(a). GAS epitope on these nucleated cells, (1) like that present on RBC, is abolished by sialidase, unaffected by proteases, and inhibited by sialyllactose; and (2) is overlapping and/or proximal to that recognized by anti-sLe(x) MoAb, CSLEX-1, and KM-93. Moreover, CAGAS binds soluble cancer-associated mucins bearing sLe(x) and sLe(a) determinants. This binding is inhibited by sialyllactose and these mucins inhibit the RBC CA activity of CAGAS. The possible significance of anti-Sia-lb (anti-Gd) CAs as autoantibodies directed to carbohydrate ligands of host adhesion molecules that might be receptors of microbial adhesins of some CA-inducing pathogens is discussed.

Agglutinins↗
PubMed1997

Inverse correlation between IgG-antihinge region and antierythrocyte autoantibody in chronic benign and malignant cold agglutination.

Previous reports provided evidence of an immunosuppressive role of natural anti-F(ab')2 antibodies. If suppressive anti-F(ab')2 antibodies also regulated the autoantibody production in cold agglutination, one would expect high titers of anti-F(ab')2 to be associated with low titers of cold agglutinins. Indeed, our previous studies revealed an inverse correlation between IgG-anti-F(ab')2 and cold agglutinins. Many previous experiments focused on anti-F(ab')2 of an antiidiotypic nature. Recent epitope mapping showed that anti-F(ab')2 of healthy persons is not an antiidiotype but recognizes a hinge region sequence. We attempted to answer the question whether this IgG-antihinge antibody is responsible for the previously described association between anti-F(ab')2 and cold agglutinins. IgG-antihinge and IgG-anti-F(ab')2 antibody was determined and statistically analyzed in the serum of 334 patients with cold agglutination. Our experiments revealed a strong correlation between the concentrations of antihinge and the previously described anti-F(ab')2 antibody. The anti-F(ab')2 activity was competitively inhibited by a synthetic hinge peptide. Moreover, patients with high antihinge titers had low cold agglutinin titers, and vice versa. A stratification according to cold agglutinin specificity and disease etiology showed that the inverse correlation is present only in anti-I and anti-i patients suffering from monoclonal B-lymphocyte proliferation. In conclusion, our results confirm the correlation previously described for anti-F(ab')2 antibody and antierythrocyte autoantibody and define for the first time an association between an idiotype-independent anti-IgG autoantibody and cold agglutinin.

Adult↗
PubMed1997

Identification of IgG alloantibodies in patients with high-titer IgM cold agglutinins by serum/plasma affinity chromatography.

The detection of IgG alloantibodies in the presence of high-titer cold autoagglutinins (CAs) can be extremely difficult, especially under pressure of time when transfusion of red blood cells is urgently needed. Here we demonstrate that IgG alloantibodies in the presence of high-titer IgM CAs can be easily detected by quantitative IgG purification from serum or plasma by affinity chromatography. In comparison with the routinely used methods for IgG alloantibody identification, affinity chromatography shows better or identical results and is the method leading to results most rapidly.

Agglutinins↗
PubMed1997

CMV-induced anti-Sia-b1 cold agglutinin in an immunocompromised patient.

In postinfection cold agglutination, certain cold agglutinin (CA) specificities are associated with distinct infectious agents. The combined occurrence of anti-I and anti-Sia-b1 CAs following Mycoplasma pneumoniae infection has been reported recently. After renal transplantation and hyperacute graft rejection, transiently occurring CAs were observed in an 18-year-old boy. The CAs were characterized by serum cold absorption with sialidase-treated red cells and warm elution from the cells. An anti-Sia-b1 CA could be differentiated from an accompanying low-liter anti-I. Fresh infections with Mycoplasma pneumoniae, Epstein-Barr virus, rubella, and varicella viruses were excluded, but CMV infection was demonstrated. This is the first case of a postinfection anti-Sia-b1 CA associated with CMV infection.

Adolescent↗
PubMed1997

Case report: anti-Coa in a Co-(a+)-typed patient with chronic renal insufficiency.

The recently identified molecular structure of the Colton blood group system is characterized by an amino acid substitution at position 45 (Colton a: alanine, Colton b: valine) of the archetypical water channel protein Aquaporin-1 (AQP1), which regulates water homeostasis in the erythrocyte membrane and in the proximal tubule of the nephron. We identified a patient with the unique constellation of an antibody with the specificity anti-Coa and the Co (a+) phenotype. The serological antigen typing was confirmed by molecular typing with PCR-RFLP. The antibody has to be interpreted as an antibody against a partial Colton a antigen or as an autoantibody despite a negative direct antiglobulin test (DAT). The patient is suffering from chronic renal insufficiency of unknown origin, rising speculation about a pathophysiological relationship between the serological constellation and the clinical disease under the aspect of localization of the Colton antigens on AQP1.

Adult↗
PubMed1997

Enhancement of Sia-lb1 antigenicity by sulphur-containing substituents at C-5 of free N-acetylneuraminic acid.

The Sia-lb1 epitope, recognized by anti-Sia-lb1 cold agglutinins, is unique since it is represented by the alpha-N-acetylneuraminic acid (alpha NeuNAc) monosaccharide. Chemical modifications of the chain at C-5 of alpha NeuNAc have shown that the natural 2-carbon and the artificial 3-carbon chains are optimal for anti-Sia-lb1 binding. Sia-lb1 antigenicity of alpha NeuNAc could be tenfold enhanced by replacement of the carbonyl oxygen by sulphur. The structural requirements of the Sia-lb1 epitope for optimal antibody binding were identified.

Agglutinins↗
PubMed1996

Structure of antigens recognized by cold agglutinins.

At this time, three major groups of antigens recognized by cold agglutinins (CAs) are known: Iij antigens are defined by branched, linear, and branched and linear type 2 chains, respectively. They are protease- and sialidase-resistant. Whereas Ii antigens are developmentally regulated, j is expressed on newborn and adult erythrocytes in equal strength. The antigens of the Sia complex are biochemically related to the Iij antigens: they are sialylated type 2 chains. Consequently, they are protease resistant but sialidase-sensitive. Sia-l and Sia-b antigens are differentiation antigens, Sia-lb is not developmentally regulated. The structure of the Pr/Sa antigens is defined by the O-glycans of the glycophorins of the human red blood cell membrane. The immunodominant component is represented by N-acetyl-neuraminic acid. Therefore, Pr/Sa antigens are protease-sensitive. With one exception (Pra), the antigens of this complex are also sialidase-sensitive. They are not developmentally regulated.

Adult↗
PubMed1996

Effect of low ionic strength on anti-Pr reactions.

The effect of low ionic strength (LIS) on 28 anti-Pr, 20 anti-I and 20 anti-i cold agglutinins was investigated. The reaction of the anti-Pr CAs varies markedly. In most cases LIS has an enhancing effect. In some cases the thermal amplitude was widened so far that the reaction at 37 degrees C under LIS was stronger than at 0 degree C in PBS. With regard to the anti-Pr subspecificities anti Pr1, -Pr2 and -Pr3 or to the distinction of the immunodominant NeuNAc group (alpha a2,6- or alpha 2,3-bond) a correlation between these characteristics and the reaction in LIS could not be identified. The anti-I are not influenced by LISS, anti-i in a few cases. The reason for the variable reaction of the anti-Pr remains unclear. To further elucidate the LISS effect on anti-Pr, the contribution of the antibody structure should be regarded, but data for the use of H- and L-chain genes in anti-Pr are sparse. For compatibility testing in the routine laboratory, LISS-sensitive anti-Pr may play a role in disturbing the screening for RBC antibodies.

Agglutinins↗
PubMed1996

[Quality assurance in transfusion medicine: organization of a quality assurance system exemplified by the Heidelberg University Blood Bank].

The 'Pharmabetriebsverordnung' requires a quality assurance system for the manufacturing of blood products. The quality assurance system of the university blood bank at Heidelberg is founded on the components 'quality of structure', 'quality of process' and 'quality of result'. The internal quality standard, based on national law and national/international guidelines, is specified in written form for every aspect of structure, process and result by standard operating procedures (SOPs). The SOPs are the basis for the quality system manual and the laboratory reference books. The quality assurance system integrates a programme for carrying out internal quality audits as well as a concept for updating SOPs at regular intervals.

Blood Banks↗
PubMed1995

Striking inverse correlation between IgG anti-F(ab')2 and autoantibody production in patients with cold agglutination.

Previous experiments showed that the physiologic IgG anti-F(ab')2 antibody suppresses the response of human autoreactive B cells. In the present study, we analyzed the IgG anti-F(ab')2 antibody in 293 patients with cold agglutination (CA). Their average IgG anti-F(ab')2 titer was not much different (211 +/- 8.3) from that of 279 healthy persons (195 +/- 6.7). However, CA patients with high anti-F(ab')2 titers had low CA autoantibody titers and vice versa (P = .0028; rho = -0.175). The stratification of patients according to the auto-antibody's specificity (anti-I, anti-i, anti-Pr) showed an inverse correlation between anti-F(ab')2 and CA in the anti-I group (P = .0057; rho = -0.180). Interestingly, the association was present only in patients whose disease was caused by noninfectious agents (P < .0001; rho = -0.423). The inverse correlation argues for an important role of the IgG anti-F(ab')2 in the regulation of autoantibody production in CA patients.

Agglutinins↗
PubMed1995

Anti-Pr cold agglutinins recognize immunodominant alpha 2,3- or alpha 2,6-sialyl groups on glycophorins.

Anti-Pr agglutinins (CAs) with the subspecificities anti-Pr1h, -Pr1d, -Pr2, -Pr3h, -Pr3d, -PrM and anti-Sa CAs recognize immunodominant N-acetylneuraminic acid (NeuN Ac) groups of tetra and/or trisaccharides (O-glycans) of glycophorin. These O-glycans are sialylated in alpha 2,3- and/or alpha 2,6-linkages. Sa and most Pr antigens have been inactivated by alpha 2,3-specific sialidases. Antigenicity was reconstituted on desialylated glycophorin by alpha 2,3-specific Gal beta 1,3GalN Ac-sialyltransferase indicating that alpha 2,3-linked NeuN Ac groups are the immunodominant components of Sa and most Pr antigens. Some Pr antigens were resistant to alpha 2,3-specific sialidase and were not reconstituted by alpha 2,3-specific Gal beta 1,3GalN Ac-sialyltransferase, which indicates that alpha 2,6-linked NeuN Ac group represents an immunodominant component of some Pr antigens.

Adult↗