IgG subclass deficiency and chronic fatigue syndrome.
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Chronic Disease↗
Biomedical subjects
C I Smith
Publications and source records attributed to C I Smith.
IgG subclass distribution of antiviral antibodies in common variable immunodeficiency: effect of substitution therapy.
Immunoglobulin G subclass titers to three herpesviruses (herpes simplex; HSV; cytomegalovirus, CMV; varicella zoster virus, VZV) were examined in patients with common variable immunodeficiency (CVI) before and after immunoglobulin substitution. Like healthy controls, CVI patients expressed IgG1 and IgG3 to HSV and CMV, but only IgG1 to VZV. Individual titers varied as in healthy individuals, but as a mean, specific IgG titers were lowered in proportion to the decrease of total IgG. HSV and CMV IgG3 titers were relatively higher than the IgG1 titers in CVI patients, resulting in a lower IgG1/IgG3 ratio than in healthy individuals (P = 0.025 and 0.05, respectively). The high IgG3 titers in CVI patients could be due to subclinical reactivations of HSV and CMV in these patients. Low VZV IgG1 and absence of IgG3 could explain the increased frequency of zoster infections reported in CVI patients. After immunoglobulin substitution, herpesvirus-specific IgG1 titers increased while HSV and CMV IgG3 decreased or remained stationary. In two unsubstituted patients, HSV and CMV titers remained stationary during 1 and 5 years, respectively, while an increase of VZV IgG1 and IgG3 indicated VZV reactivation although the patients remained asymptomatic.
Adult↗
Ontogeny of immunoglobulins in bone marrow-transplanted individuals. An analysis of serum and salivary levels.
Unstimulated whole saliva and serum samples were collected from ten allogeneic bone marrow transplant recipients before and after bone marrow transplantation, seven donors, and from twenty healthy individuals. Two patterns with regard to salivary IgA were found after transplantation. In five patients, a short-lasting peak of excessive IgA production was noted shortly after BMT. Two of these patients had an increase of both secretory and the nonsecretory form of IgA, whereas the other three only demonstrated elevated nonsecretory IgA levels. After the IgA peak the IgA level decreased below the level before BMT. In five patients a different pattern was seen, with a marked decrease in salivary IgA, IgG, and IgM as well as albumin after grafting. A highly variable pattern of reconstitution was seen after one year, when three out of seven patients were still deficient in secretory IgA.
Adolescent↗
An analysis of pulmonary natural killer cell activity in F1-hybrid mice with acute graft-versus-host reactions.
The kinetics of activation, cell surface phenotype, target cell specificity and anatomic localization of pulmonary natural killer cells was examined in (C57BL/6 X A/J)F1-hybrid mice with acute graft-versus-host reactions induced by intravenous injection of 50 x 10(6) parental strain lymph node and spleen cells. Results showed that there was a marked increase in NK cell activity directed against YAC-1 tumor cells. This activity remained elevated in the lung over almost the entire course of the reaction, whereas it was only transiently increased in the spleen during the early stages of the reaction and then fell to control values. During the reaction, NK cells from both organs acquired the ability to kill P815 targets, cells that are normally insensitive to NK cell lysis. The level of P815 killing never reached that achieved against YAC-1 cells, but was significantly higher in the lung than in the spleen. Antibody and complement depletion experiments showed that both anti-YAC-1 and anti-P815 activity could be depleted with antiserum to the asialo-GM1 cell surface marker, but was unaffected by anti-Lyt-1.2 and anti-Lyt-2.2 treatment. Anti-YAC-1 activity was partly sensitive to depletion with anti-Thy-1.2. Cytotoxicity to P815 target cells acquired during the reaction was completely abrogated by anti-Thy-1.2. These findings suggest that during the reaction two phenotypically distinct types of NK cells are activated: a conventional, Thy-1-negative cell that kills only YAC-1 targets, and a Thy-1-positive cell with a broadened spectrum of lytic activity. We suggest that the latter may be generated in response to interleukin-2 released during the lymphoproliferative phase of the reaction and may represent a type of lymphokine-activated killer cell. Our results revealed that virtually all of the NK cell activity in the lung could be attributed to cells residing in the interstitium, or to cells tightly adherent to endothelium or epithelium. There was no correlation between augmented NK cell activity in the lung and the presence of peribronchial and perivascular mononuclear cell infiltrates seen in histological sections of the lung. These findings do not appear to support the idea that NK cells are by themselves directly responsible for the pathological changes produced by the reaction.
Acute Disease↗
Anti-DNA antibody synthesis after bone marrow transplantation: implications for IgG subclass restrictivity and pathogenicity of autoantibodies.
Two patients developed antinuclear antibodies (ANA) including antibodies directed against double-stranded DNA (dsDNA) after bone marrow transplantation. In one of the patients very high levels of IgM, IgG as well as IgA anti-dsDNA were found during 6 months in the absence of symptoms of systemic lupus erythematosus (SLE). The other patient made IgM anti-dsDNA antibodies for a period of more than 3 years, also in the absence of SLE symptoms. The ANA were restricted to the IgG1 and IgG3 isotypes as is the case in SLE but did not express idiotypes commonly found in this autoimmune disease. The occurrence of these antibodies may reflect a non-antigen induced expansion of the existing donor B-lymphocyte repertoire.
Antibodies, Antinuclear↗
The antibody spectrum in individuals with defect expression of HLA class II and the LFA-1 glycoprotein family genes.
HLA class II antigens and the LFA-1 (lymphocyte function-associated type 1) glycoprotein family are cell surface structures of central importance in many lymphocyte reactions. Specific antibodies are normally restricted to particular IgG subclasses. In order to study the mechanism of isotype restriction we have analysed specific IgG1, IgG2, IgG3 and IgG4 antibodies directed against a number of different protein and polysaccharide antigens in individuals with HLA class II or LFA-1 deficiency. HLA class II deficiency resulted in decreased total IgG2, IgG4 and IgA in 4/4 patients, whereas total IgM and IgG were low in 2/4. In HLA class II deficiency the levels of specific antibodies directed against protein as well as polysaccharide antigens were frequently low. Virtually normal total as well as specific antibody levels were found in individuals with both severe and moderate forms of LFA-1 deficiency. There was no clear evidence for an abnormal subclass pattern of specific antibodies with a shift from one subclass to an isotype which is normally not used, in any of the patient groups investigated.
Adult↗
The IgG1 subclass preference of selected, naturally occurring antipolysaccharide antibodies.
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Adult↗
Subclass distribution and IgE responses after treatment in human schistosomiasis.
The IgG and IgA subclass distribution of specific antibodies as well as the distribution of total and specific IgE in 15 patients with schistosomiasis was determined in consecutive samples before and after initiation of treatment. An adult worm antigen preparation and a soluble egg antigen preparation were used as antigens in the ELISA assays. After initiation of treatment a rise was noted in certain subclasses and a correlation was found for specific IgG1 and IgG4 serum levels in the egg-excreting patients against adult worm antigen and for specific IgG4 and IgE levels in sera from the eight patients with a chronic disease. They also had a rise of the specific IgA1 titre and six of them also of specific IgA2. Members of eosinophilic granulocytes reached a peak after 2 weeks in seven of the eight patients. The increase of eosinophils was an early event as opposed to the incidence of peak of the determined specific isotypes. The associated rise in IgG1, IgG4 and IgE antibody concentrations and eosinophils may suggest a causal relation possibly induced by common interleukins.
Adolescent↗
The sequential appearance of IgG subclasses and IgE during the course of Trichinella spiralis infection.
Earlier studies have shown that IgG1 and IgG4 are the dominant IgG subclasses in the specific response during a chronic helminthic infection. It has also been suggested that IgG4 production results from chronic or repetitive antigenic stimulation and a correlation between IgG4 and IgE levels exists. An outbreak of Trichinella spiralis infection in Poland provided the opportunity to follow the sequential appearance of the IgG subclass and IgE responses in 15 patients during the early stage of Trichinella infection and to compare these observations in sera obtained one year later from the same patients. The results show that the sequential appearance of the IgG subclasses were IgG1 before IgG3 and IgG3 before IgG4. IgG1 antibodies dominated the immune response in all patients. A statistically significant increase in the number of IgG4 positive sera was observed in patients during the chronic stage compared to the findings during the early stage of infection (13% vs 73%; p less than 0.001), supporting the view that IgG4 results from a chronic antigenic stimulation. A correlation between the appearance of IgG4 and IgE was not found. The highest levels of IgE were seen in the first serum samples obtained, with a decrease during the course of infection.
Adolescent↗
Strategies for codon usage in human VH families.
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Codon↗
Evidence of hepatitis virus infection among Australian prisoners of war during World War II.
A sample of Australian male veterans of World War II was surveyed after 40 years. One hundred and seventy veterans had been held by the Japanese as prisoners of war and 172 veterans had served in southeast Asia but had not been taken captive (non-prisoners of war). A medical history was obtained and a physical examination undertaken. Blood was drawn and analysed for standard liver biochemistry and serological markers of hepatitis A and B virus (HAV, HBV) infections. The prevalence of immunoglobulin (Ig)G class antibodies to HAV was 95.2% in non-prisoners of war and 93.3% in prisoners of war. Only three cases of hepatitis B surface antigen (HBsAg) seropositivity were identified (two cases from the prisoner-of-war group). Thirty-six (21.8%) prisoners of war were seropositive for the presence of antibodies to HBsAg (anti-HBs) and 34 (20.0%) prisoners of war for that of antibodies to hepatitis B core antigen (anti-HBc), compared with 16 (9.8%) and eight (4.7%) of the non-prisoners of war, respectively (P = 0.002 and P = 0.0001, respectively). Those veterans who reported jaundice during World War II had a higher prevalence of antibodies to HBV. Among prisoners of war who were forced to work on the Burma-Thailand railway, 24.1% were seropositive for anti-HBc compared with 11.1% of the remaining prisoners of war (P = 0.048). It would appear that hepatitis B was common in prisoners of war but that those who survived 40 years were able to clear the virus and do not appear to have significant liver disease.
Asia, Southeastern↗
The use of human antigen-specific monoclonal antibodies in an enzyme-linked immunosorbent assay for the determination of anti-HBsAg antibody subclasses.
A human monoclonal anti-HBsAg antibody (IgG1, lambda) was used as a reference for an ELISA determination of the serum levels of anti-HBsAg antibodies in human volunteers after vaccination with H-B vax. The IgG subclass distribution of specific antibodies showed a marked dominance of IgG1 antibodies. In addition, small amounts of specific IgG4 antibodies were occasionally found, suggesting a different pattern from that found after natural disease. The novel use of a human monoclonal antibody to measure specific antibodies may give a more accurate determination of specific IgG subclass levels than previously available methods.
Antibodies, Monoclonal↗
Human T-cell tumours containing chromosome 14 inversion or translocation with breakpoints proximal to immunoglobulin joining regions at 14q32.
T-cell tumours are frequently found to carry an inversion of chromosome 14 (inv(14)) (q11;q32) or more rarely a chromosome 14 translocation t(14;14) with the same cytogenetic breakpoints (q11;q32). We have examined the molecular junctions of an inv(14) and a translocation t(14;14) using T-cell receptor (TCR) alpha joining (J) region probes. Both of these chromosomal abnormalities have breakpoints within the TCR J alpha locus at 14q11 and both have breakpoints which are proximal (i.e. on the centromeric side) to the immunoglobulin heavy chain JH region at 14q32. The cloned segments corresponding to the junctions at 14q32 are not associated with obvious immunoglobulin-like sequences. This contrasts to the previously described inv(14) in the cell line SUP-T1 and places a potential cluster of chromosome 14 breakpoints downstream of the Ig JH locus. The possible role of the varying breakpoints in the development of these tumours is discussed.
Amino Acid Sequence↗
Immunoglobulin prophylaxis in patients with antibody deficiency syndromes and anti-IgA antibodies.
Sera from three hundred five patients with immunoglobulin deficiencies were analyzed for the presence of anti-IgA antibodies by using indirect agglutination and enzyme-linked immunosorbent assay (ELISA). Anti-IgA antibodies were observed in 15 of 68 (22%) patients with hypogammaglobulinemia and 53 of 185 (29%) patients with selective IgA deficiency, both groups having serum IgA less than 0.05 g/liter. The highest frequency, 6 of 10 or 60%, was noted for patients with a combined IgA-IgG2 deficiency. No anti-IgA antibodies were detected in 25 patients with serum IgA between 0.05 and 0.27 g/liter and normal amounts of serum IgM and IgG or in 17 patients with hypogammaglobulinemia who had serum IgA of 0.05-0.7 g/liter. The anti-IgA antibodies were primarily of the IgG class, but IgD and IgM anti-IgA were occasionally found. IgE anti-IgA antibodies could not be detected with the presently used technique. The IgG anti-IgA antibodies were mainly of the IgG1 subclass but occasionally also of the subclasses IgG2, IgG3, and IgG4. Of eight patients with anti-IgA antibodies, seven tolerated Ig prophylaxis with a commercial immunoglobulin preparation low in IgA when given either intramuscularly or intravenously. The titers of anti-IgA in the sera of these patients did not rise in relation to the prophylaxis. Only one of the eight patients had a history of previous anaphylactic reactions to IgA-containing blood products. He tolerated six Ig infusions during 5 months with the IgA-depleted preparation without any adverse effects but showed increasing levels of anti-IgA antibodies and ultimately experienced a near-fatal reaction at the seventh infusion.
Antibodies, Anti-Idiotypic↗
Subclass restriction pattern of antigen-specific antibodies in donors with defective expression of IgG or IgA subclass heavy chain constant region genes.
We have developed a method for the measurement of the IgG and IgA subclass distribution of antigen-specific human antibodies. The controls for the specificity of the assay include the use of a number of monoclonal human antibodies and sera from individuals with deletions of particular immunoglobulin heavy chain constant region genes. The system was used to determine the shift in immunoglobulin subclass patterns of specific antibodies against a variety of protein and polysaccharide antigens in individuals with a regulatory deficiency of a given IgG or IgA subclass. Normally, the pattern is quite distinct and antibodies against protein antigens are mainly of the IgG1 subclass, whereas antibodies against polysaccharide antigens are mainly of the IgG2 subclass. The results on serum from an IgG1 deficient donor suggested that IgG3 and IgG4 appear to compensate for a lack of IgG1, whereas isolated deficiencies of IgG3, IgG4, or IgA2 do not markedly influence the expected distribution of specific antibodies. In IgG2-deficient individuals a more complex pattern was observed where antibodies against protein antigens were retained, whereas levels of antibodies against polysaccharide antigens could vary markedly between donors, which appeared to be dependent on whether the IgG2 deficiency was an isolated defect or combined with IgG4/IgA deficiency. However, all the IgG2-deficient donors had a skewed pattern of anti-polysaccharide antibodies with a shift to IgG1 to IgG3.
Antibodies↗
Frequent occurrence of monoclonal gammopathies with an imbalanced light-chain ratio following bone marrow transplantation.
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Anemia, Aplastic↗
Generation of the antibody repertoire in individuals with multiple immunoglobulin heavy chain constant region gene deletions.
Antibodies against protein antigens are largely restricted to the IgG1 subclass in man, whereas anti-carbohydrate antibodies, at least in adults, are almost exclusively confined to the IgG2 subclass. In IgG2-deficient donors where the C gamma 2 gene is retained in the genome, antibodies against most polysaccharide antigens are absent. We therefore undertook a study of the antibody repertoire in 11 adult donors with immunoglobulin heavy chain constant region gene deletions, homozygous or heterozygous defects, encompassing the C gamma 2 gene. In all cases, antibodies against polysaccharide antigens were present and restricted to the remaining subclasses (IgG1 and/or IgG3). These results suggest an unrestricted use of the available VH gene repertoire in donors lacking the C gamma 2 gene, and imply that the limited antibody repertoire found in IgG2-deficient individuals with a retained C gamma 2 gene may be a consequence of an altered regulatory mechanism or a structural VH gene defect. However, furthermore, the deletion of multiple C gamma heavy chain constant region genes did not appear to decrease the IgG switch probability as such, since total serum levels of IgG appear to be normal.
Antibody Formation↗
Immunoglobulin subclass distribution of specific antibodies in allergic patients. Prediction of the IgE inducing capacity of potential allergens.
The IgG and IgA subclass distribution of specific antibodies against a variety of protein and polysaccharide antigens was determined in sera from individuals with high levels of IgE. No shift of the antibody pattern could be observed, suggesting that the aberrant regulation of responses against allergens noted in these patients is limited, encompassing selected antigens only. Antibodies against protein antigens are mainly of the IgG1 subclass. In addition, low levels of specific IgG3 or IgG4 antibodies may be formed. Our data suggest that a given antigen induces either IgG3 or IgG4 and that potential allergens, in addition to IgG1 and IgE, elicit a response restricted to IgG4.
Antibodies, Anti-Idiotypic↗