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.     

Increased frequency of HLA-A1 and -B8 in association with total lack, but not with deficiency of serum IgA

HLA-A, B, C typing was performed on 37 unrelated healthy blood donors with selective deficiency (<0.05 g/l) or total lack (<0.00002 g/l) of serum IgA. A significant increase in HLA-B8 and A1 antigen frequency was found in the 15 individuals with lack of serum IgA. This was not observed among those 22, who had only deficiency of serum IgA (0.00002–0.05 g/l). The HLA antigen frequencies were compared to those of 900 randomly selected healthy blood donors.
Increased frequency of HLA-A1 and B8 in association with total lack of serum IgA, but not with deficiency has not been demonstrated before. On the basis of this result it seems conceivable that lack of serum IgA may be caused by a different, perhaps genetically determined, mechanism that IgA deficiency.     

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.     

Studies on HLA antigens and cellular and humoral autoimmune phenomena in patients with myasthenia gravis.

The HLA phenotype of fifty-four patients with myasthenia gravis (MG) was compared to that of 600 controls. When male and female patients were compared separately with the control group, HLA-B12 was increased in MG males (P less than 0-023) and HLA-A1, B8 in MG females (P less than 0-023). In addition, HLA-A1, B8 was correlated with the early onset type of MG and with a more severe clinical course (Osserman scale IIb-III) in female patients. Cell-mediated immune responses were studied in a twenty-one hospitalized MG patients. Specific cell-mediated immunity to highly purified muscle proteins was investigated using the two-step-leucocyte migration agarose test and general cell-mediated immunity was studied by determining the cutaneous response to four extrinsic antigens. Cellular immune activity to muscle antigens occurred in fourteen out of twenty-one patients (67%) with MG and with one exception, in none of the controls. There was no significant difference in the LIF inducing ability of the different muscle antigens. A statistically significant correlation between HLA-A1 and B8 and either cell-mediated immune reactivity to muscle antigens or humoral autoimmune phenomena or clinical parameters was not found. Only a trend toward an association between HLA-A1 and B8 and a cell-mediated immune response to muscle antigens could be demonstrated. Positive delayed skin reactions to extrinsic antigens were observed with the same frequency as in healthy blood donors.     

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.     

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-A*9, a probable secondary susceptibility marker to ankylosing spondylitis in Basque patients

HLA-B27 is strongly associated to ankylosing spondylitis (AS). The objective of our study was to analyze HLA-B27 association, B27 subtype distribution and frequency of other HLA class I and DR antigens in a group of Basque AS patients. HLA class I antigens were typed serologically and HLA-B27 and A9 subtypes were determined by DNA typing in samples from 46 patients with AS, 54 B27-positive spondyloarthropathies, 82 healthy subjects and 20 B27-positive controls. A class I HLA 9.2 kb PvuII restriction fragment length polymorphism (RFLP), previously associated with AS, was analyzed in a representative group of patients and controls. We found that HLA-B*2705 conferred a relative risk of 126 for AS in this group. HLA-A9 (A*2402) allele was significantly increased in AS patients compared with healthy controls and B27-positive control group (Pcorr<0.0001) and also increased in patients affected with peripheral arthritis. No association between class I HLA 9.2 Kb RFLP and AS was found. These results suggest that HLA-A*9 allele itself or another linked gene could act as a secondary and independent susceptibility allele to AS.     

HLA association of anti-IgA antibody production

We have HLA typed 46 unrelated IgA deficient blood donors in our region. A weak association to DR3 (RR = 2.07) was observed. However, owing to the heterogeneous nature of this group, we found DR7 may be associated with those who developed class-specific anti-IgA antibodies (RR = 2.94), whereas DR1 may be associated with those who did not (RR = 2.42).     

HLA association of idiopathic Peyronie's disease: an indication of autoimmune phenomena in etiopathogenesis?

HLA typing for class I and class II antigens was done in 52 unrelated patients suffering from idiopathic Peyronie's disease. The controversially discussed association with the HLA-B7 cross-reacting group could not be confirmed. Marked deviations of antigen frequencies were observed for HLA-A1, B8, Cw7, DR3 and DQw2 compared to healthy local controls. After correction of p-values, A1 (pc less than 0.05) and DQw2 (pc less than 0.01) remained significant. A possible association of Peyronie's disease with markers of the HLA-A1, B8, Cw7, DR3, DQw2 haplotype, as first described here, would suggest autoimmunological factors in this disorder of otherwise unknown etiopathogenesis.     

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-associated non-responsiveness to Hepatitis B vaccine

HLA-A,B,DR antigens of two groups, one of normal individuals (N- = 31) and another of CRF (Chronic Renal Failure) patients (K- = 37), who did not develop anti-HBs protective antibodies after Hepatitis B (HB) vaccination, were compared, respectively, to the HLA antigens of two corresponding control groups (N+ = 52, K+ = 49), who responded to the vaccine. A statistically significant difference (Pc less than 0.02) in the frequency of HLA-DR3 was observed between responders and non-responders. An increased frequency of HLA-A1 and HLA-B8 in N- as well as of HLA-A1 and HLA-B35 in K- was also noticed, but this was not of statistical significance. As these antigens have been associated to both HBs antigenemia as well as chronic active hepatitis, we suggest that these genes or other genes in linkage to those may suppress the response to HBV vaccination while, in parallel, they may predispose to an autoimmune course of Hepatitis.     

Protective and susceptible HLA polymorphisms in IgA nephropathy patients with end-stage renal failure

Idiopathic immunoglobulin A (IgA) nephropathy is characterised by an extreme variability in clinical course, leading to end-stage renal failure in 15-20% of adults. This subgroup of patients with IgA nephropathy is usually included in the waiting lists of organ exchange organisations. The frequency of HLA-A,B,DR antigens of this subset of IgA nephropathy patients was calculated and compared to controls. The antigens HLA-B35 and DR5 were significantly increased in the patients with relative risk values of 1.385 and 1.487, respectively. The antigens HLA-B7, B8, DR2, and DR3 were found in a significantly lower frequency in the patients as compared to the controls. The relative risk (RR) values ranged between 0.695 and 0.727. Consequently, the haplotypes HLA-A1, B8, DR3, HLA-A3, B7, DR2, HLA-A2, B7, DR2 together with HLA-A1, B15, DR4, HLA-A9, B12, DR7, and HLA-A10, B18, DR2 were found to be protective with RR values ranging from 0.309 to 0.587. The only susceptible haplotype observed was HLA-A2-B5, DR5 (RR=2.990).     

Application of the particle gel agglutination assay in the typing of single human leucocyte antigens

We describe a simple and rapid particle gel agglutination assay (PaGIA) for typing of the human leucocyte antigens (HLA) HLA-A2, HLA-B7 and HLA-B27. Superparamagnetic streptavidin particles were coated with biotinylated monoclonal antibodies (MoAbs) to HLA-A2, HLA-B7 and HLA-B27. Anticoagulated whole blood samples from healthy blood donors (n = 118) with known HLA patterns were incubated with MoAb-coated particles, transferred into a standard ID-gel card, and subsequently centrifuged. Samples were evaluated macroscopically, with antigen-positive samples resulting in a visible agglutination reaction. A clear distinction could be made between all positive and negative samples tested. Fifty-seven samples were found to be positive for HLA-A2 (48%), 26 samples for HLA-B7 (22%) and 5 samples for HLA-B27 (4%).     

HLA-A, B, C antigens in pulmonary sarcoidosis in Polish population.

The aim of this study was to analyze association between HLA class I antigens and sarcoidosis in Poland. HLA-A, B, C antigens in a group of 100 patients suffering from sarcoidosis and in a group of 100 healthy blood donors were determined. Histocompatibility typing was performed by the NIH method using commercially available sera. For statistical analysis chi2 test was used after Yates' correction. The relative risk was calculated by Woolf's method. We found that HLA-B8 and -Cw7 prevalence was significantly higher in patients with sarcoidosis than in healthy controls. HLA-B35, -B40, -Cw2 and -Cw4 antigen expression was significantly lower in pulmonary sarcoidosis than in the tested group of healthy individuals. The highest relative risk of sarcoidosis was connected with HLA-B8 and -Cw7. The results obtained suggest that, in the population suffering from pulmonary sarcoidosis in nothern Poland, as compared with the control group of healthy persons, antigens HLA-B8 and -Cw7 are significantly more frequent. It can be assumed that, the presence of these antigens may be connected with a greater risk of pulmonary sarcoidosis. In the group of patients, as compared with the control population, the occurrence of antigens HLA-B35, -B40, -Cw2 and -Cw4 is significantly more rare.     

HLA antigens and Graves' disease in Black South Africans

This study concerns the frequencies with which 36 HLA-A, -B and -C antigens occurred in 84 Black Africans with Graves' disease and in 311 Black controls. In the hyperthyroid patients significant reductions were found in the frequencies of HLA-B7 ( P <0.001, relative risk (RR) 0.33), HLA-Bw42 ( P <0.001, RR 0.32) and the HLA-B7-Bw42 crossreactive group (CREG) ( P <0.0001, RR 0.27), and in the frequencies of the phenotypic combinations HLA-A1, B7 ( P <0.001) and Aw30, B7-Bw42 ( P <0.001). HLA-B8 was increased in frequency ( P <0.01, RR 2.84). In patients without circulating antithyroglobulin or antimitichondrial antibodies the frequencies of HLA-A2 and B17 were increased when compared to those with antibodies or to the controls. In patients with and without clinically evident infiltrative ophthalmopathy the frequencies of HLA antigens were similar. In 62 Caucasian patients with Graves' disease, no antigens or phenotypic combinations occurred with increased or decreased frequency when compared to 278 controls.
Analysis of the frequencies of 9 HLA antigens and phenotypic combinations common in Caucasians but rare in Blacks revealed that only two antigens (A2 and B8) occurred with increased frequency in Black patients, suggesting that a contribution of Caucasian genes to the Black thyrotoxic subjects was unlikely.
Similarly, only one common Black antigen (A28) of 8 common antigens and phenotypic combinations, occurred in Caucasian patients with a frequency similar to that of Black controls. Thus it is unlikely that Black genes contributed to the lack of a significant increase of HLA antigens in the Caucasian thyrotoxic patients. The possession of HLA-B7-Bw42 CREG or related genes may be a protection against Graves' disease in Black Africans.     

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.     

Immunogenetic studies of juvenile dermatomyositis

Typing for HLA-A and -B antigens was performed on 87 children with definite juvenile dermatomyositis (JDMS). A significantly increased frequency of HLA-B8 (estimated relative risk = 2.8, Pc less than 0.01) was observed among White patients, but not among Blacks or Latin Americans with JDMS. No abnormality of HLA haplotype segregation was observed among 38 healthy siblings of the JDMS probands.     

Histocompatibility (HLA) antigens and diabetic microangiopathy.

To gain further insight into the genetic determinants of diabetic small vessel disease, we studied 22 HLA antigens in 110 juvenile-onset, insulin-dependent diabetics with terminal glomerulosclerosis and retinopathy, who were being prepared for kidney transplant. HLA antigens were comtemporarily determined in non-diabetic kidney transplant recipients and healthy controls. The frequency of antigens A1 and B8 were significantly higher in diabetics than in controls (P less than .02 and .011), but the frequency of BW15 was normal. The data are compatible with the concept that juvenile diabetes with microangiopathy is one of the HLA-B8 associated disorders.     

Association between HLA phenotype and HLA concentration in plasma or platelets

To understand the relationship between HLA phenotype and plasma or platelet HLA better, concentrations of plasma and platelet HLA were measured in 215 individuals of known HLA phenotypes. Precise quantitation of HLA antigens was achieved by means of an enzyme-linked immunoassay using the W6/32 monoclonal antibody and purified HLA molecules. The mean plasma and platelet HLA concentrations were 2.04 +/- 1.67 micrograms/ml (+/- SD, n = 215) and 11.28 +/- 4.65 fg/cell (+/- SD, n = 213), respectively. Statistical analysis of associations between HLA phenotypes and plasma HLA revealed that the mean plasma HLA concentration of individuals with HLA-A23 or HLA-A24 was 1.4 (p less than 0.002) or 1.9 (p less than 0.001) times higher than those without these two HLA antigens. Furthermore, the mean plasma HLA concentration of individuals who have HLA-A26 was 25% less than those without HLA-A26 (p less than 0.05). In contrast, the only association between HLA phenotypes and HLA concentrations of platelets was observed in HLA-B7-positive individuals. The mean platelet HLA concentration of HLA-B7 individuals was 27% higher than those without HLA-B7 (p less than 0.005). This finding is in accordance with previous observations made on red blood cells. The results indicate that the HLA concentrations in plasma are regulated, at least in part, by genetic factors that are different from those regulating platelet HLA.     

中华(上海)骨髓库北方人群HLA多态性调查

调查中华(上海)骨髓库北方人群HLA多态性及其频率分布特征。用微量淋巴细胞毒试验检测11995名无关供者HLA-A、B抗原,并用PCR-SSP和反向PCR-SSOP技术对疑难标本进行复检。计算其中3 736名北方人群 HLA-A、B的抗原频率、基因频率和HLA-A、B位点单倍型频率、连锁不平衡参数。调查中共检出A位点抗原26种,B位点抗原54种,最常见HLA-A、B抗原包括A2,A11,A24,A30,A33,B13,B46,B51,B58,B60,B61,B62等。连锁不平衡参数大于0.0005的单倍型有40多种,最常见的单倍型有A2-B46,A30-B13,A33-B58等。结果显示中华(上海)骨髓库北方人群HLA多态性有自身特点,频率分布介于南、北汉族之间。