IgA Subclasses Research Articles

Antibody to Mycobacterium tuberculosis 65 kDa heat shock protein in patients with rheumatoid arthritis--a survey of antigen-specific antibody isotypes and subclasses in an endemic area of previous tuberculosis infection.

To clarify the significance of the humoral immune response triggered by the Mycobacterium tuberculosis (M.tb) 65 kDa heat shock protein (hsp) in the pathogenesis of rheumatoid arthritis (RA). M.tb 65 kDa hsp-specific IgG, IgA, IgM, and IgG subclass antibodies in serum or synovial fluid (SF) of RA and other disease patients were determined by enzyme linked immunosorbent assay (ELISA). RA patients did not show any characteristic increase in mycobacterial 65 kDa hsp-specific antibodies compared with healthy individuals. In contrast, antigen-specific IgG and IgG2 antibody titres in the serum of RA patients were significantly lower than those of patients with tuberculosis and normal controls. In addition, there was also no significant difference in antibody titre between the serum and SF of RA patients, nor was any significant difference found between the SF of RA and Reiter's patients. The failure to detect a significant increase in IgG anti-M.tb 65 kDa hsp antibodies in RA patients does not exclude the possibility of microbial immunity in the aetiology of RA. Nevertheless, anti-M.tb 65 kDa hsp antibodies clearly do not appear to be the disease specific markers for RA and their relatively reduced concentrations may argue against their playing a major role in the disease pathogenesis.

Demonstration of specific high‐affinity Fcɛ‐receptors on the human basophil‐like leukemia cell line KU812 by flow cytometry

The specificity of IgE binding to a human basophil-like cell line (KU812) was studied by flow cytometry. Four IgE myeloma proteins, representing both light-chain types, one chimeric IgE protein, and polyclonal serum IgE blocked the direct binding of FITC-labeled IgE(DES) myeloma protein to KU812 cells in a dose-dependent and nearly equimolar way. Although not as efficiently as human IgE (from five to eight times less on a molar basis), both rat and mouse IgE blocked IgE(DES)-FITC binding to KU812 cells. In sharp contrast, all four human IgG subclasses, both IgA subclasses, and IgM myeloma proteins, as well as monomeric and heat-aggregated polyclonal human IgG, were unable to block significantly IgE(DES)-FITC binding to KU812 cells (< 0.5% on a molar basis). The cytophilic epitope on IgE was heat-susceptible (56 degrees C, 2 h), lost after reduction alkylation, and resident in the papain-derived Fc epsilon-fragment, but not in the papain-derived Fab epsilon- and Fc'epsilon-fragments nor in the pepsin-derived F(ab')2 epsilon- and Fc"epsilon-fragments. Washing and displacement experiments indicated that a major part of IgE reacted with high affinity to KU812 cells. The results indicate that the binding of IgE to KU812 cells is highly specific and involves the classical high-affinity Fc epsilon RI-receptor. Although the density of receptors is low, this human cell line offers a unique model to study IgE/Fc epsilon RI interactions.

Antisperm antibodies in infertile women: subclass distribution of immunoglobulin (Ig) A antibodies and removal of IgA sperm-bound antibodies with a specific lgA1 protease

To determine the immunoglobulin (Ig) A subclass distribution of antibodies in the serum and cervical mucus (CM) of infertile women and to evaluate the effect of an IgA1 protease on the removal of sperm-bound antibodies. Twenty infertile women with antisperm antibodies in serum (n = 10) or in CM (n = 10) were recruited for this study. Monoclonal antibodies to human IgA1 and IgA2 were conjugated to immunobeads and the IgA subclass distribution of antisperm antibodies was determined for positive serum and CM samples. The effect of an IgA1 protease (isolated from Neisseria meningitidis strain HF13) on sperm-bound antibodies was evaluated by immunobead binding. In serum, IgA1 subclass antisperm antibodies predominated (89%) when compared to IgA2 (11%). In CM IgA1 accounted for 62% and IgA2 accounted for 38% of the total IgA antisperm antibodies. Enzyme treatment was able to reduce dramatically the amount of serum IgA antibodies bound to sperm from 88% to 10%. Similarly, a significant reduction in CM antisperm antibodies was observed after enzymatic treatment with no loss in sperm motility. Cervical mucus antisperm antibodies have a higher proportion of IgA2 subclass suggesting a local production of IgA. Specific IgA1 protease treatment is capable of reducing the amount of immunobead-detectable IgA on sperm. Hamster sperm penetration assays are ongoing to determine if this treatment might improve sperm penetration rates with antibody positive sperm.

Carbohydrate heterogeneity of human myeloma proteins of the IgA1 and IgA2 subclasses

Comparative studies of the N-linked carbohydrate chains of human myeloma proteins of the IgA1 and IgA2 subclasses were performed. The N-linked carbohydrate chains were released by hydrazinolysis from the polypeptide backbone, converted to radioactive oligosaccharides by sodium borotritide reduction after N-acetylation and separated into one neutral and two acidic fractions by paper electrophoresis. The acidic oligosaccharides were completely converted to neutral oligosaccharides by sialidase treatment, indicating that they were sialyl derivatives. The neutral and sialidase-treated acidic oligosaccharides were further fractionated by Bio-Gel P-4 column chromatography. Structural studies of each oligosaccharide by sequential exoglycosidase digestion and methylation analysis revealed that human myeloma IgA proteins contained significant amounts of biantennary complex-type carbohydrate chains in addition to a small amount of the high mannose-type. The results indicated that the oligosaccharide structures of human IgA1 and IgA2 display a high degree of heterogeneity not only in the number of carbohydrate chains, but also in their composition.

Passively transferable protection against Schistosoma japonicum induced in the mouse by multiple vaccination with attenuated larvae: the development of immunity, antibody isotype responses and antigen recognition.

Vaccination of mice with attenuated S. japonicum cercariae induces protection against secondary infection which can be transferred to naive mice with serum (VMS). The presence of antibody does not per se impart protection as serum from mice carrying non-attenuated infections (CIS), contains high levels of specific antibody, but confers no protection. Here we describe the increased protection transferred (20 to 68%) with increased number of vaccinations (one to five) given to the donors, and its decline with time after the final vaccination. We also describe the development of IgM, IgA, IgE, total IgG and IgG subclass responses in VMS, giving different levels of protection and CIS, directed against sodium periodate-sensitive and -resistant epitopes in 'skin-stage', 'lung-stage' and 'liver-stage' schistosomula, adult worms and eggs. In addition, antibody affinity maturation, development of S. japonicum species-specific responses, and vaccination-specific responses were examined. No response developed in parallel with serum-mediated immunity, suggesting immunity may be due to responses against individual antigens. Preliminary examination of antigens recognized in Western blot showed that two schistosomal membrane antigens, of 13 and 40 kDa, were recognized by VMS from mice vaccinated five times (68% protection), but not by twice vaccinated VMS (27% protection). Neither antigen was recognized by non-protective CIS.

Increased immunoglobulin A and immunoglobulin A1 cells in bone marrow trephine biopsy specimens in immunoglobulin A nephropathy.

The origin of mesangial immunoglobulin A (IgA) in IgA nephropathy remains unknown. To investigate potential abnormalities within the bone marrow in this condition, bone marrow trephine biopsy specimens from seven patients and matched controls were studied using two-color immunofluorescence. In addition, serum levels of IgA and IgA1 were determined by radial immunodiffusion. Serum levels of IgA and IgA1 were higher in patients than in controls (4.53 +/- 1.38 g/L v 2.56 +/- 1 g/L, P < 0.01 and 3.68 +/- 1.11 g/L v 1.92 +/- 0.7 g/L, P < 0.005, respectively). In addition, patient trephine biopsy specimens contained an increased percentage of IgA plasma cells (61.6% +/- 4.4%) compared with controls (47.3% +/- 2.5%) (P < 0.02). The proportion of IgA plasma cells bearing subclass IgA1 was also greater in the patient biopsy specimens (91.6% +/- 1.9%) compared with controls (81.4% +/- 2.7%) (P < 0.01). In patients a positive correlation between the percentage of marrow IgA plasma cells and serum IgA levels was found (r = 0.94, P < 0.002). However, our studies failed to demonstrate a similar correlation between serum IgA1 levels and IgA1 marrow cells. These findings support the hypothesis that mesangial IgA may derive from the bone marrow.

Validation of IgA1 and IgA2 measurements by a solid-phase immunoradiometric assay in serum and secretions.

We describe specific, sensitive and reproducible immunoradiometric assays to measure total IgA and IgA subclass levels in biological fluids, which take into account the problem that polymeric forms are differently recognized in immunoassays. Sera from subjects totally deficient in one of the IgA subclasses allowed us to ensure the specificity of the subclass assays and to define the proportions of IgA1 (84%) and IgA2 (16%) in the normal pooled serum (from 30 blood donors) used as standard. With purified milk 11-S secretory IgA1 and 11-S secretory IgA2, we determined a correction factor for the corresponding polymeric forms using, respectively, monomeric IgA1 and monomeric IgA2 from pooled serum as standards. With the monoclonal antibodies used, purified 11-S secretory IgA1 was similarly recognized by both the total IgA assay and the IgA1 assay; both total IgA and IgA1 concentrations were underestimated compared with monomeric IgA or monomeric IgA1. In contrast, 11-S secretory IgA2 was better recognized by the IgA2 assay than by the total IgA assay and the values were thus overestimates. Considering this problem of recognition, we fractionated saliva and lung secretions by sucrose density gradient ultracentrifugation before measuring their IgA1 and IgA2 levels.

Differential effects of gangliosides on Ig production and proliferation by human B cells

The effects of gangliosides on human B-cell responses were studied. Of various gangliosides tested, only GM2 and GM3 inhibited production of IgG subclasses and IgM, but not IgA subclasses, and thymidine uptake by human B cells stimulated with SAC plus interleukin-2 (IL-2). In contrast, GM1, GD1a, GD1b, GD3, GT1b, and GQ1b were without effects. GM2- and GM3-induced inhibition were specific, because each was blocked by a corresponding antibody. Of various cytokines tested, tumor necrosis factor-alpha (TNF-alpha) alone counteracted GM2- and GM3- induced inhibitions of Ig production and thymidine uptake, whereas other cytokines including IL-1 beta, IL-3, IL-5, IL-6, and interferon- gamma each failed to do so. Moreover, anti-TNF-alpha antibody, but not control IgG, blocked the counteraction of inhibition by TNF-alpha. GM2 and GM3 each inhibited Ig production, thymidine uptake, and TNF-alpha production by surface IgG1+ (slG1+), sIgG2+, sIgG3+, sIgG4+, and sIgM+ B cells without affecting IL-2 binding or TNF-alpha binding to B cells, but had no such inhibitory effects on sIgA1+ or sIgA2+ B cells. These findings indicate that GM2 and GM3 inhibit Ig production and thymidine uptake by human sIgG1+, sIgG2+, sIgG3+, sIgG4+, and sIgM+ B cells by inhibiting endogenous TNF-alpha production.

Differential Effects of Gangliosides on Ig Production and Proliferation by Human B Cells

The effects of gangliosides on human B-cell responses were studied. Of various gangliosides tested, only GM2 and GM3 inhibited production of IgG subclasses and IgM, but not IgA subclasses, and thymidine uptake by human B cells stimulated with SAC plus interleukin-2 (IL-2). In contrast, GM1, GD1a, GD1b, GD3, GT1b, and GQ1b were without effects. GM2- and GM3-induced inhibition were specific, because each was blocked by a corresponding antibody. Of various cytokines tested, tumor necrosis factor-alpha (TNF-alpha) alone counteracted GM2- and GM3-induced inhibitions of Ig production and thymidine uptake, whereas other cytokines including IL-1 beta, IL-3, IL-5, IL-6, and interferon-gamma each failed to do so. Moreover, anti-TNF-alpha antibody, but not control IgG, blocked the counteraction of inhibition by TNF-alpha. GM2 and GM3 each inhibited Ig production, thymidine uptake, and TNF-alpha production by surface IgG1+ (slG1+), sIgG2+, sIgG3+, sIgG4+, and sIgM+ B cells without affecting IL-2 binding or TNF-alpha binding to B cells, but had no such inhibitory effects on sIgA1+ or sIgA2+ B cells. These findings indicate that GM2 and GM3 inhibit Ig production and thymidine uptake by human sIgG1+, sIgG2+, sIgG3+, sIgG4+, and sIgM+ B cells by inhibiting endogenous TNF-alpha production.

Intestinal mucosal immunoglobulins during human immunodeficiency virus type 1 infection.

In intestinal fluid samples from 39 human immunodeficiency virus type 1 (HIV-1)-infected patients, IgA and IgG levels were equivalent, whereas in 10 controls, IgA levels were significantly higher than those of IgG (P < .05). Intestinal IgA in patients contained predominantly monomeric IgA1, whereas IgA1 and IgA2 subclass levels in controls were nearly equivalent and primarily polymeric. The predominance of IgG and monomeric IgA1 in mucosal fluid samples from HIV-1-infected patients suggests exudation of serum immunoglobulins into the intestine. The decreased proportion of mucosal plasma cells producing IgA and IgA2 in the HIV-1-infected patients (P < .01) may also contribute to the abnormal intestinal immunoglobulin levels. Intestinal IgG reacted with most HIV-1 antigens, whereas specific IgA was present in only 10 of 17 patients and reacted with only envelope (gp120 and gp160) and, less often, core (p17 and p24) antigens. Aberrant mucosal antibody responses and decreased integrity of the mucosal barrier may contribute to the intestinal dysfunction and infections that characterize HIV-1 infection.

Immunoglobulins and IgG subclasses in children following severe head injury

To study immunoglobulin production after severe blunt head trauma in children. Serum for IgG, IgM, IgA, IgE, and IgG subclasses were drawn from 10 children admitted with severe head injury (ISS 31.2, GCS 5.4) on day 1, 7, 14 and 21 after injury. 5 of the 10 patients developed infection between 7 and 14 days and 2 died of complications of pneumonia. On day 1, IgM levels averaged 95.6% of the mean of the age-specific normal controls. By day 7, IgM levels averaged 383% (p < 0.01). While all patients were within the age-specific normal range (+/- 2 SD) on day 1, 7 of 10 patients were above the normal range by day 7. There was no difference in IgM levels between infected and non-infected patients. Five patients were below the age-specific normal range for IgG on day 1, with 3 still low on day 7. By day 21, IgG levels averaged 141% of the mean of the age-specific normal controls. IgG subclasses followed a pattern similar to total IgG levels. Marked increases in IgE were seen in 3 patients. IgM levels increased dramatically in all patients within seven days of the injury. While 50% of these children had a deficit of IgG in the first week, total IgG and IgA levels increased after injury, but not as rapidly as IgM levels. Unlike pediatric burn patients, there is no persistent hypogammaglobulinemia following severe blunt trauma in children.

Yersinia-specific antibodies in serum and synovial fluid in patients with Yersinia triggered reactive arthritis.

To further evaluate the role of bacterial antigens in triggering inflammation in the joint in patients with reactive arthritis by studying local antibody synthesis in the joint. Yersinia-specific antibodies in paired serum and synovial fluid samples from 29 patients with yersinia triggered reactive arthritis were studied using an enzyme linked immunosorbent assay (ELISA), an inhibition ELISA with six monoclonal antibodies against lipopolysaccharide or released proteins of yersinia and immunoblotting. Antibodies of IgM, IgG and IgA classes, as well as antibodies of IgA subclasses and those containing secretory component were measured against the lipopolysaccharide and the sodium dodecyl sulphate extract of whole Yersinia enterocolitica O:3 bacteria. It was shown that yersinia-specific antibodies, as well as antibodies against other microbial antigens (rubella, measles, Bordetella pertussis, tetanus toxoid and Candida albicans) in synovial fluid mirror those in serum by concentration, by specificity and by distribution in classes and subclasses. These results do not suggest any strong local antibody production, but indicate that the majority of yersinia antibodies in the synovial fluid are derived from the circulation.

Is there IgA of gut mucosal origin in the serum of HIV1 infected patients?

This study was performed in 77 HIV1 seropositive adult patients to characterise the IgA hyperglobulinaemia seen in the serum during the course of HIV infection. It was shown that both IgA1 and IgA2 subclass concentrations were simultaneously increased but the IgA1 increase was predominant. Secretory IgA (SIgA) concentration was significantly increased and IgA activity to gliadin, bovine serum albumin, and casein could be detected and was correlated with SIgA concentration. In contrast, IgA activity to cytomegalovirus and to tetanus toxoid did not correlate with total IgA concentration. These data suggest the presence of IgA from gut mucosal origin in the serum of these patients. Hyper IgA was inversely correlated with the CD4+ cell number. The increase of all parameters studied varied according to the total IgA concentration in the serum but was also directly related to the stage of immune deficiency in patients with hyper IgA.

Immunoglobulin A subclasses in infants' saliva and in saliva and milk from their mothers

We sought to determine (1) the ontogeny of secretory IgA subclasses in saliva of breast- and formula-fed infants and (2) the influence of breast-feeding on the maturation of secretory salivary IgA subclasses. Secretory IgA and subclasses 1 and 2 concentrations were determined in saliva from 40 healthy, term infants from birth to age 18 months, and in parallel milk samples from the infants' mothers who were breast-feeding during the first 6 months after birth. Secretory IgA was detected in the neonates' saliva as early as 3 days after birth, increased rapidly during the next 6 months, but then stabilized at a level approximately one-sixth that of the mothers' salivary secretory IgA. Secretory IgA2 represented less than 15% of secretory IgA in saliva collected 2 weeks after birth but by 6 months represented 24.4% of secretory IgA, a value approaching that of the mothers' salivary secretory IgA2 (30.4%). This increase in the proportion of secretory IgA2 was temporally related to a reduction in the proportion of secretory IgA2 in milk throughout lactation. The secretory IgA concentration increased more rapidly during the first 6 months after birth in infants exclusively breast fed than in those exclusively bottle fed. We conclude that although secretory immunity is immature in infants, breast-feeding may aid in protection against pathogenic microorganisms by increasing the rate of mucosal IgA maturation.

Antisperm antibodies (ASAs) in infertile males: subclass distribution of IgA antibodies and the effect of an IgA1 protease on sperm-bound antibodies.

(1) To determine the IgA subclass distribution of antibodies in the serum and on the sperm of infertile male patients. (2) To determine the effect of an IgA1 protease on the binding of IgA antisperm antibodies (ASA). Fifteen infertile males with ASA in serum (10) or on sperm (5) were recruited for this study. Duration of infertility was at least one year. Monoclonal antibodies to human IgA1 and IgA2 were conjugated to immunobeads. The distribution of IgA1 and IgA2 subclass ASA was determined for positive serum and sperm samples. The effects of an IgA1 protease (isolated from Neisseria meningitidis strain HF13) on sperm-bound antibodies was evaluated by immunobead binding. In serum, the IgA1 subclass ASA was predominate (91%) when compared with IgA2 (9%) subclass. Direct sperm-bound antibodies displayed a distribution more characteristic of the secretory immune system with IgA1 accounting for 63% and IgA2 accounting for 37% of the total IgA ASA. Enzyme treatment dramatically reduced the amount of serum IgA antibodies bound to sperm (P < 0.05). Similarly, a significant reduction in direct sperm-bound antibodies was observed after enzymatic treatment with no loss in sperm motility. (1) Although IgA1 direct sperm-bound antibodies were dominant, when compared with serum there was a higher proportion of IgA2 subclass, which suggests a local production of IgA. (2) Specific IgA1 protease treatment is capable of reducing the amount of immunobead-detectable IgA on sperm. Hamster oocyte sperm-penetration assays are ongoing to determine if this treatment might improve sperm penetration rates.

Trypanosoma cruzi infection in mice induces a polyisotypic hypergammaglobulinaemia and parasite‐specific response involving high lgG2a concentrations and highly avid lgG1 antibodies

Trypanosoma cruzi infection in BALB/c mice induced a reversible polyisotypic hypergammaglobulinaemia, with particularly high levels of IgG2a, IgM and IgE. Hypergammaglobulinaemia started during the acute phase of infection and persisted during chronic disease until 11-13 weeks post-infection (w.p.i.), when immunoglobulin levels, with the exception of IgE, returned near normal values. Parasite-specific antibodies counted for 14 to 23% of gammaglobulinaemia, in acute and chronic infection respectively. The titres of IgM antibodies rose from two w.p.i. IgA, IgE and IgG subclass antibodies built up gradually over the time of parasite clearance (i.e., between three and six w.p.i.). All antibody isotypes, including IgM reached significant and stable titres throughout chronic infection. IgG2a, IgG1 and IgM antibodies had constantly higher titres than the other antibody isotypes. The dominance of IgG2a antibodies was due to their high plasma concentrations, around 70% of all antibodies available in the chronic infection. IgG1 had the highest functional avidity, whereas its concentration corresponded to only 10% of the whole antibody fraction. These results indicate that T. cruzi infection in mice induces a polyisotypic humoral immune response, dominated by some antibody isotypes, with major differences in concentrations and functional avidities. This could be of crucial importance in determining the outcome of infection.

Charge distribution of IgA-lambda in IgA nephropathy.

The finding that eluted mesangial IgA and serum IgA from patients with IgA nephropathy had a restricted anionic charge contrasting with normal serum IgA prompted us to study the charge of the kappa and lambda subclasses of IgA. Serum IgA from 11 patients with IgA nephropathy and 11 controls was purified by affinity chromatography by binding to jacalin. The charges of IgA were studied by a novel method. The spectrotype of total IgA was first studied by isoelectric focusing and immunoblotting. IgA lambda and IgA kappa was further analyzed by reacting with specific monoclonal antibodies. The amount of IgA with different pIs was analyzed by computerized densitometry. The anionic:cationic (A:C) ratio of IgA using pI 5.6 as the dividing point was greater in patients (at clinical quiescence and during exacerbation) than in controls (1.67 +/- 0.31 versus 1.36 +/- 0.27, p < 0.025). IgA lambda in both groups was anionic (A:C ratio 2.22 +/- 0.77 versus 2.36 +/- 0.36) and IgA kappa was cationic (A:C ratio 1.15 +/- 0.36 versus 1.04 +/- 0.39) but no difference in the A:C ratio was demonstrated. The increased A:C ratio in total IgA in patients was due to raised serum IgA lambda (kappa/lambda ratio 1.11 +/- 0.14 in patients and 1.51 +/- 0.16 in controls, p < 0.01). We had previously shown a predominant mesangial deposition of IgA lambda in IgA nephropathy. Animal experiments have revealed the preferential mesangial deposition of immune complexes is related to their anionic charges. Our data of raised anionic IgA lambda in IgA nephropathy may be important in determining its selective mesangial binding that could contribute to the immunopathogenesis.

An early humoral immune response in peripheral blood following parenteral inactivated influenza vaccination

The enzyme-linked immunospot assay was used to examine the humoral immune response in 15 healthy volunteers immunized with either split or subunit inactivated trivalent influenza vaccine containing A/Beijing/353/89 (H3N2), A/Taiwan/1/86 (H1N1) and B/Yamagata/16/88. The rapidity of the individual B-cell and serum antibody response was examined in lymphocyte and serum samples collected at various time intervals after vaccination. A rapid serological response was detected with increases in antibody titre detected in the majority of volunteers by 7–8 days postvaccination. Influenza-specific plasma cells were detected as early as 4 days postvaccination, higher numbers of IgA and IgG antibody-secreting cells (ASC) were observed which peaked at 7–8 days postvaccination. The number of ASCs then declined, with low numbers of cells detected at 11 days postvaccination. Influenza-specific IgA ASCs were predominantly of the IgA1 subclass. This rapid immune response may have a bearing on future vaccination policies of unimmunized ‘at risk groups’ in times of high influenza activity.

Etiology of IgA nephropathy syndrome.

Since Berger's original paper on mesangial IgA-IgG deposition with hematuria, there have been a number of clinical and pathological studies regarding IgA immune complexes, the mechanisms of glomerular IgA deposition leading to glomerular injury and animal models of IgA nephropathy. During the last quarter of this century, glomerular changes such as IgA nephropathy have also been observed in cases associated with other diseases, such as systemic lupus erythematosus, Schoenlein-Henoch purpura, liver cirrhosis and chronic inflammatory diseases of the lung. This evidence supports the idea of an IgA nephropathy syndrome. On the other hand, IgA is thought to be an important humoral factor at the mucosal immune system and appears to have an antibody function against various etiologic candidates of extrinsic or intrinsic substances at the mucosal and systemic immune system. Glomerular IgA deposition in IgA nephropathy syndrome is thought to result from elevated levels of circulating immune complexes or aggregated IgA due to an overproduction of polymeric IgA as antibodies in the serum and due to the clearance impairment of IgA immune complexes in the hepatic and splenic phagocytic system. The glomerular IgA subclass is not one-sided, but should be evaluated in comparison with the age of patients at renal biopsy; this indicates the approximate age of onset. Cirrhotic IgA glomerulonephritis is not related to Hepatitis B or C virus infection, but to the pathophysiologic condition of liver cirrhosis. Various etiologic candidates such as viral, microbial, dietary antigens or auto-antigens have been listed and experimental models of IgA nephropathy syndrome have provided some clues in understanding the etiology of primary IgA nephropathy. However much still remains to be clarified and some specific epitopes common among these etiologic candidates will have to be identified.

Immunochemical characterization of the anti‐B response in an ABO‐incompatible blood transfusion: presence of antibodies recognizing glucosylceramide

Summary. A male patient of blood group A was accidentally given two units of group B blood when operated upon because of injury. This resulted in an immediate haemolytic transfusion reaction. The patient was treated with exchange transfusions in order to remove the incompatible red cells and thus prevent renal damage. Two weeks after the transfusion, an anti‐B humoral immune response appeared. The antibodies were mainly IgG and IgA types, of IgG3 and IgA1 subclasses. The anti‐B antibodies seemed specific for the B trisaccharide [Galα1–3(Fucα1–2)Gal] as tested by radioimmunoassay and chromatogram binding assay. No antibodies recognizing part of the core saccharide chain could be detected, i.e. antibodies capable of differentiating between B type 1 and B type 2 chains did not occur. An unsuspected finding was that the patient had IgG antibodies recognizing glucosylceramide (and weakly also galactosylceramide) before and after the transfusion. These antibodies were still present 9 years after the ABO‐incompatible blood transfusion.