HLA-A, B, C and DR antigens in immunoglobulin A deficiency

HLA-A, B, C and DR typing was performed in 21 unrelated healthy blood donors with selective IgA deficiency (< 0.02 G/l of IgA). A significant increase in HLA A1 ( P < 0.05), HLA B8 ( P < 0.01) and HLA DR3 ( P < 0.001) was found. The frequency of HLA A28 was also increased ( P < 0.05). Furthermore, HLA A28 was present in all four donors lacking DR3.     

HLA and IgA deficiency in blood donors

We have identified 67 IgA deficient healthy blood donors in our region by systematic screening of 24,782 blood samples. HLA typing results on 36 of these donors indicated a significant association with both HLA-A1 and HLA-B14 antigens. The frequency of A29 and B8 antigens was also increased. However, B8 association may be secondarily involved due to linkage disequilibrium (e.g., A1-B8-DR3). The frequency of HLA-A1 and HLA-B8 antigens was increased in the group of IgA deficient donors who developed anti-IgA antibodies (53.9%) compared to those who did not (26.1%). Although the sample size appears to be too small to show a statistical significance (chi 2 = 2.76, 0.05 less than p less than 0.1), this is the first report to imply a possible HLA association with anti-IgA antibody formation by IgA deficient healthy individuals.     

HLA antigens in selective IgA deficiency: Distribution in healthy donors and patients with recurrent respiratory tract infections

HLA-A, B, C and DR typing was performed in healthy IgA deficient donors and in IgA deficient patients with recurrent respiratory tract infections. In healthy donors, a strong association with HLA B8 and DR3 was observed. In the patient group however, no statistically significant association with these antigens could be found. In contrast, an increased frequency of HLA B40 was noted. The preference for HLA B8/DR3 in healthy donors could not be attributed to higher levels of serum immunoglobulins since no major differences in the concentrations of IgM, IgG or the IgG subclasses were seen between the two groups.     

Long-term follow-up of health in blood donors with primary selective IgA deficiency

A 20-year health follow-up study of 159 initially healthy blood donors with a severe deficiency of serum IgA (<0.05×10^–3 g/L) and of 45 donors with decreased serum IgA (0.05×10^–3–0.8 g/L) was carried out. The findings indicate that persons with a severe deficiency of and decreased serum IgA who are healthy as young adults have an increased susceptibility to pneumonia and recurrent episodes of other respiratory infections and a higher risk of developing autoimmune diseases in middle age. Vitiligo, autoimmune hypothyreosis, milk intolerance, and possible rheumatoid arthritis were associated with severe IgA deficiency, but otherwise different degrees of IgA deficiency seem to be similar with respect to the appearance of diseases. Regardless of the fact that a total of 163 (80%) of the 204 IgA-deficient subjects had episodes of infections, drug allergy, or autoimmune or atopic disease, the finding of primary, selective IgA deficiency in a healthy adult per se does not seem to predict severe life-threatening illnesses at least during 20 years of life.     

Association of IgA deficiency with HLA A28 and B14

HLA typing was performed in two groups of individuals with low serum IgA concentrations. These consisted of 44 individuals identified from a blood donor clinic and 37 individuals attending an Immunology clinic with disorders associated with IgA deficiency. Both groups showed an increase in the frequency of HLA B14 (p less than 0.0001), HLA-A28 (P = 0.0007) and the combinations HLA-A1, B14 and HLA-A28, B14. The previously reported increase in HLA-A1, B8 was not apparent in either group. These data suggest that there is a gene within the human major histocompatibility complex which is relevant in IgA deficiency.     

The concentrations of IgA and free secretory piece in the nasal secretions of patients with recurrent respiratory infections.

The concentrations of total IgA, 11S IgA, total and free secretory piece (SP) were measured in the nasal secretions of 39 patients with recurrent upper and lower respiratory tract infections during an infection free period. In all of eight patients who had selective serum IgA deficiency (less than 0.05 g/l) IgA was also undetectable in their nasal secretions and the mean concentration of free SP was significantly raised. However, the mean concentrations of 11S IgA, SP and free SP in nasal secretions of patients with normal or low (greater than 0.05 g/l but below the normal range) serum IgA were not significantly different from those of 10 healthy normal subjects. In patients with detectable nasal secretory IgA, 11S IgA concentrations correlated significantly (r = 0.57; P less than 0.001) with concentrations of free SP. One patient with normal serum IgA was found to have a large excess of free SP and therefore may have had a relative defect in local IgA production.     

IgA deficiency in Czech healthy individuals and selected patient groups

BACKGROUND: Selective IgA deficiency (IgAD) is the most common immunoglobulin deficiency with a variety of clinical manifestations. The frequency of IgAD differs depending on the ethnic origin and clinical symptoms of investigated persons. METHODS: The prevalence of IgAD (serum IgA level <0.05 g/l) was determined in 5,310 Czech blood donors, 10,326 patients who had undergone immunological investigation, and 246 first-degree relatives of IgAD and common variable immunodeficiency (CVID) patients. RESULTS: IgAD was detected in 13 (1/408; 0.24%) of the blood donors. The prevalence of IgAD was increased both in children (48/3,113; 1.5%) and adults (33/3,824; 0.9%) referred for frequent respiratory tract infections (in both cases p<0.001) compared to the healthy population. The frequency of IgAD was 12/189 (6%) in first-degree relatives of IgAD patients and 9/57 (16%) in relatives of CVID patients, with the highest frequency observed in children of CVID patients. CONCLUSIONS: The prevalence of IgAD in the Czech healthy population is comparable to that in other Caucasians. The frequency is increased in children with recurrent respiratory tract infections and especially in relatives of patients with immunoglobulin deficiencies.     

HLA antigens in IGA deficient paediatric patients

HLA antigens (A, B, C and DR loci) were studied in 62 IgA-deficient (IgAd) paediatric patients: 17 with coeliac disease (CD), 13 with juvenile arthritis (JA), 27 with frequent respiratory tract infections (RTI) and five with other diseases. The frequencies of HLA antigens in IgAd patients were compared with those in healthy blood donors, and in CD and JA patients with normal serum IgA levels. The IgA deficiency in the patients showed significant associations with HLA A1, B8, B13, Cw6, DR3 and DR7 (P less than 0.0005, P corr less than 0.02 vs controls) and decreased frequencies of DR2 (P less than 0.0005, P corr less than 0.02 vs controls). The HLA associations typical of coeliac disease, increased frequencies of HLA-B8 and DR3, were evident among the IgAd coeliacs; in contrast to the coeliacs with normal IgA levels, the IgAd coeliacs showed a significant increase of the HLA-Cw6 allele (P less than 0.0005, P corr less than 0.02 vs control coeliacs). Increased frequencies of HLA-A1, B8, B13, Cw6, DR3 and DR7 were noted in the patients with RTI, which can be explained by the frequent occurrence of the haplotypes A1, B8, DR3 and B13, DR7, the latter haplotype often also having the Cw6 allele. Among the IgAd JA patients, the antigen frequencies were similar to those in the JA patients with normal serum immunoglobulins.     

Anti-IgA antibodies in epileptic patients with a low serum IgA concentration

Sera from 22 phenytoin-treated epileptic patients with a serum IgA less than 0.30 g/l were examined for anti-IgA antibodies using an ELISA. Only one patient had a complete IgA deficiency. Anti-IgA antibodies of restricted specificity were detected in serum from two of the patients. Their serum IgA concentrations were 0.03 and 0.27 g/l. The serum concentrations of IgM, IgG and the IgG subclasses were normal in both these patients. The frequency of this type of anti-IgA antibody is not higher in epileptic patients with a low serum IgA than in healthy controls, and class-specific anti-IgA antibodies are not a pathogenetic factor in the IgA deficiency occurring in epilepsy.     

Long-term follow-up of anti-IgA antibodies in healthy iga-deficient adults

A follow-up study of anti-IgA antibodies in 159 healthy blood donors with severe deficiency of serum IgA (<0.05 mg/L) and in 45 donors with decreased serum IgA levels (0.05–799 mg/L), identified in 1971–1980, was carried out. Initially anti-IgA antibodies were determined by a hemagglutination (HA) method and two reexaminations were done in 1990–1992 by an enzyme immunoassay. The median follow-up period was 19 years, during which anti-IgA level was changed considerably in only four persons, increased in two, and high level antibodies (>1/1000 by HA) appeared in two. In reexaminations anti-IgA antibodies were found in 30 (19%) subjects with severe IgA deficiency and the antibody levels remained relatively constant in those who had high and medium antibody levels. Anti-IgA antibodies were not found in subjects with decreased, but detectable serum IgA. Thus it seems that only those healthy adults who have severe IgA deficiency develop anti-IgA antibodies and their anti-IgA levels remain fairly constant Of the 159 subjects with severe IgA deficiency, 66 had a history of IgA exposure, but no correlation to anti-IgA development was noted.Portions of the work have been presented in a poster form at the XXIIIrd Congress of the International Society of Blood Transfusion in Amsterdam, the Netherlands, July 2–9, 1994.     

Food antibodies, intestinal permeability and HLA status in IgA deficient blood donors identified by a new rapid screening test

Abstract. Circulating food antibodies, intestinal permeability and HLA status were studied in twelve blood donors previously identified as being selectively IgA deficient from screening 10 000 donations by means of a latex agglutination inhibition test, and confirmed by laser nephelometry. Assessment of intestinal function also included clinical history and standard laboratory tests. The donors proved to be healthy with no evidence of autoimmune disease or allergy. Nine donors (75%) had precipitins to food antigens. None had increased intestinal permeability as measured by the cellobiose/mannitol absorption test. HLA-A, B and DR antigen distribution was normal. IgG sub-class distribution was normal with the exception of an IgG2 level slightly below normal in one donor (0·9 g/1). An unexpected finding was a return of IgA levels to normal in four donors (33%) within 6 months.     

HLA-DR7 in children with idiopathic nephrotic syndrome.: Correlation with atopy

Idiopathic nephrotic syndrome (INS) of childhood is likely to be underlain by an immunopathological mechanism; we investigated the presence of immunogenetic HLA markers in this disease. Fifty-four unrelated INS-affected children, among them 20 with an allergic status, were studied for 33 HLA-A,B and 6 HLA-DR antigens. The results were compared to those obtained in 49 children with glomerulonephritis, 28 children with atopy but without nephropathy, and 91 healthy blood donors. The HLA-A and B antigen frequencies were not significantly different from normal frequencies. The incidence of HLA-DR7 was significantly increased in INS-affected patients as compared to the other groups (66.7% in patients vs 31.1% in healthy controls; corrected P value < 0.001; relative risk = 4.4), and more so in those with atopy than in those without atopy (90% vs 46%; P = 0.002). The frequency of this antigen is not increased in atopic non-nephrotic children. No relationship between HLA-DR7, clinical outcome and steroid-responsiveness was found. We suggest that the pathogenesis of INS could be influenced by an HLA-linked immune response gene, especially in its atopy associated form.     

Gm allotypes in IgA deficiency

Gm phenotypes were examined in 90 Swedish IgA-deficient (less than 0.05 g/litre of serum IgA) donors and 40 normal first and second degree relatives of six of these donors. The G1m1,2, G3m5 and Km1 frequency in the group of IgA-deficient donors did not differ from that found in the normal population. Among the relatives, HLA and/or Gm identical normal sibs were observed. Anti-IgA antibodies were present in 29 of the IgA-deficient donors and anti-IgG in seven. No association between the two was found. A statistically significant association between the G1m-2 phenotype and the presence of anti-IgA antibodies was observed. When subdivided according to HLA type, a non-random distribution of Gm phenotypes was seen in HLA-B8/DR3 positive individuals with anti-IgA antibodies (HLA-B8/DR3 being the haplotype associated with IgA deficiency). These data suggest an association between IgA deficiency, anti-IgA and the studied Gm allotypes.     

Serological HLA class I alleles in Senegalese blood donors detected HBs Ag positive

We analysed the HLA class I alleles in 96 blood donors HBs Ag positive compared with 93 healthy control individuals (HBs negative). The most frequent HLA-A, -B, -C alleles found were, A23 (33.6%); A2 (25%); A30 (25%); B8 (31.5%); B7 (16.3%); B58 (11.9%); B35 (11.9%); B49 (11.9%); B53 (10.8%); Cw7 (39.1%); Cw3 (36.9%); Cw4 (36.9%). Significant differences (P<0.001) were found between the blood donors and the controls for the following HLA alleles, A1; A23; B8 and Cw3. The detection of HBe antigen was positive in 26/84 blood donors. It was observed a significant difference (P<0.01; odds ratios (OR)=6.25) between positive and negative HBe antigens blood donors for HLA-A1 allele.     

Detection of enterovirus-specific total and polymeric IgA antibodies in serum using a synthetic peptide or heated virion antigen in ELISA

The presence of enterovirus-specific total and polymeric IgA antibodies was assessed in serum from different groups of patients and healthy controls by indirect ELISA using heated virions and synthetic peptide, both enteroviral broad reactive antigens. Total IgA antibody response against a synthetic peptide, representing an enterovirus group-common epitope, was detected in 52% of the patients with an acute enterovirus infection and in 12% of the patients with other infections (P = 0.02). We also found a significant difference (P = 0.005) in the prevalence of peptide IgA antibodies between serum samples collected from blood donors during summer (20%), the prevalent season of enterovirus infections, and winter (6%). A polymeric IgA activity against the peptide was detected in only three patients with an enterovirus infection. In contrast, when a heated coxsackie B5 (coxB5) virus antigen was used, the prevalence of total serum IgA antibodies was not significantly different between patients with an acute enterovirus infection and patients with other infections (71 % vs. 53% respectively; P = 0.3). Also no difference was found between the two groups of blood donors (47% in summer vs. 51% in winter; P = 0.7). However, the prevalence of serum polymeric IgA antibodies against coxsackie B5 antigen was significantly greater (P = 0.02) in patients with an acute enterovirus infection (57%) than in patients with other infections (18%). These findings suggest that the presence of total peptide-IgA or of polymeric coxsackie B5-IgA in serum is a specific marker of acute enterovirus infection. Finally, we show that the total peptide-IgA-and polymeric coxsackie B5-ELISAs may have a diagnostic value for the serodiagnosis of enterovirus infections when they are used in combination with enteroviral IgG-ELISA. © 1994 Wiley-Liss, Inc.     

Functional assessment of a B cell defect in patients with selective IgA deficiency

The cellular basis of selective IgA deficiency was investigated by examining the terminal differentiation of B lymphocytes co-cultured with varying ratios of T lymphocytes in the presence of pokeweed mitogen. Eight patients were studied who had serum IgA concentrations <0·05 mg/ml, salivary IgA <0·01 mg/ml, and between 0·8 and 4% lymphocytes with surface IgA markers. Peripheral blood lymphocytes from patients and normal donors were separated into B cell (non T cell) and T cell fractions by E-rosetting. Microcultures were established at eleven B cell to T cell ratios from 100% B cells to 100% T cells. After 7 days, immunoglobulin in the supernatant fluid was measured by radioimmunoassay. Cultures containing patients' B cells and either autologous or allogeneic T cells produced very low or undetectable amounts of IgA. However, cultures from six out of eight patients contained cells with intracytoplasmic IgA. Secretion of IgM by the patients' B cells was identical to that of normal donors. Surprisingly, IgG production by patients' B cells was less than that produced by normal B cells especially in the mid-range ratios of the microcultures. Production of IgA, IgG and IgM by normal B cells from peripheral blood or tonsils was very similar in the presence of normal T cells or patients' T cells. In cultures containing optimal ratios of normal B cells, the patients' T cells not only did not suppress IgA production but also gave normal help for IgA production. It was concluded, on the basis of these studies, that a defect in patients with selective IgA deficiency was the functional inability of their B cells to produce normal amounts of IgA in vitro even when provided with normal allogeneic T cell help.     

IgA Deficiency and the MHC: Assessment of Relative Risk and Microheterogeneity Within the HLA A1 B8, DR3 (8.1) Haplotype

Introduction  

Selective IgA deficiency (IgAD; serum IgA concentration of <0.07 g/l) is the most common primary immunodeficiency in Caucasians with an estimated prevalence of 1/600. The frequency of the extended major histocompatibility complex haplotype HLA A1, B8, DR3, DQ2 (the “8.1” haplotype) is increased among patients with IgAD.     

乙型肝炎患者血清免疫球蛋白检测的意义

目的 分析乙型肝炎患者血清免疫球蛋白检测的意义。方法 选取本院2016年8月~2018年3月120例确诊为乙型肝炎的患者作为观察组,对其临床资料进行回顾性分析,同时选取120例健康体检者作为对照组,对比两组受检者血清免疫球蛋白检测结果。结果 观察组IgG、IgM、IgA水平分别为（15.63±2.63）g/L、（2.97±0.98）g/L、（2.97±1.62）mg/L均高于对照组的（11.05±1.08）g/L、（1.52±0.27）g/L、（1.81±0.27）mg/L,差异有统计学意义（P＜0.05）;通过对比120例患者治疗前后相关指标可以发现,治疗好转者IgG、IgM、IgA、TBLI水平均低于病情恶化者,差异有统计学意义（P＜0.05）。结论 对于乙型肝炎患儿患者而言,实施血清免疫球蛋白检测的价值明显,既能对患者病情严重程度加以判断,还能为乙型肝炎的诊断和治疗提供可靠依据。     

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<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.     

Long-term persistence of selective IgA deficiency in healthy adults

A follow-up study of 204 healthy blood donors with IgA deficiency, identified between 1971 and 1980, was carried out. Sera were initially screened by a double diffusion method and 182 were retested by a more sensitive haemagglutination inhibition method. A reexamination was performed in 1990 and, again, in 1991–1992 using an enzyme immunoassay (EIA) developed for the measurement of very low concentrations of IgA. The median follow-up period was 19 years, and in 159 (78%) subjects no serum IgA could be detected in any of the measurements. In 42 (21%) subjects, serum IgA was detectable (>0.18 mg/L), but the level was below the lower limit of the reference range for adults (800 mg/L) and remained relatively constant. Three subjects showed minute amounts of IgA by EIA (0.2–3 mg/L) in one of the follow-up samples in 1990–1992, but the level was below the detection limit of the EIA (0.05 mg/L) in the other sample. Thus, not only does primary IgA deficiency appear to be permanent, but also lower than normal serum IgA levels remain the same in healthy adults.Portions of this work were presented in poster form at the XIVth Meeting of the European Society for Pediatric Hematology and Immunology in Oulu, Finland, September 7–10, 1993.