Chromosomal studies in healthy blood donors with IgA deficiency

Chromosomal analysis was performed in 70 asymptomatic blood donors found over a 5-year period in a large screening programme to be IgA deficient. No abnormalities were found in any of these individuals in relation to their chromosomal constitution and, in particular, chromosome 18 was normal in all individuals. A further 10 symptomatic individuals with IgA deficiency also showed a normal chromosomal constitution with no abnormalities of chromosome no. 18.     

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.     

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.     

HLA gene and haplotype frequencies in Dutch blood donors

We analyzed the HLA-A, -B, -C, -DR and -DQ phenotypes of 2,440 healthy, unrelated, Dutch Caucasoid blood donors and of 20, 814 Dutch blood donors who were registered as volunteer bone marrow or platelet donors. Phenotype and gene frequencies, Hardy-Weinberg equilibrium fit and homozygosity were calculated as well as 2- and 3-locus haplotype frequencies, deltas, relative deltas and significance levels of the deltas. The population appears to be in Hardy-Weinberg equilibrium. Many haplotypes are in strong positive linkage disequilibrium. A phylogenetic tree, based on the HLA-A, -B and -DR gene frequencies of blood donors in different Dutch regions, reflects the limited but manifest heterogeneity of the Dutch population. Additionally we introduce a stepwise test for Hardy-Weinberg equilibrium and discuss the applicability of this test and of the single test for Hardy-Weinberg equilibrium for tissue typing quality control and for selection of split antigens prior to gene and haplotype frequency analyses.     

Recurrent extended HLA haplotypes in children with selective IgA deficiency

HLA supratypes as well as serum IgG, IgA and IgM levels were determined in 44 children and adolescents with severe IgA deficiency (serum IgA less than 5 mg/dl) and in first degree relatives. Frequencies of the HLA alleles B14, DR1, DQW1, C4A2 and C4B2 were significantly higher in the IgA-deficient patients than in the controls. The most recurrent haplotype among patients was B14, DR1 (p less than 10(-4) preferentially associated with A33, A28 or A blank. The supratype B14, Bfs, C4A2, C4B2, DR1, DQW1 was present in a 14-fold higher frequency than in the controls, and strongly suggests the presence of a gene in the HLA region involved in the deficiency of IgA. The fact that this supratype was not always associated with IgA deficiency in the parents and that not all IgA-deficient subjects had this supratype is discussed. Severe IgA deficiency was found in four mothers (two of the four mother-child pairs shared the B14, DR1 haplotype); three other relatives (one father and two brothers) had partial IgA deficiency and did not have the B14, DR1, DQW1 haplotype.     

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.     

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 recognition of Hageman deficiency in blood donors

The laboratory findings on a blood donor whose blood coagulation time was greatly prolonged are described. The defect was caused by a deficiency of Hageman (contact) factor, the nature of the defect being demonstrated by a simple glass adsorption test using normal serum.     

Screening of blood donors for IgA deficiency: a study of the donor population of south-west England.

Altogether 29 745 English blood donors were screened for IgA deficiency by double diffusion analysis; 57 had apparent absence of IgA, a frequency of 1:522. Further examination by the more sensitive haemagglutination inhibition assay revealed 34 samples having no detectable IgA, a frequency of 1:875. All donors negative by double diffusion analysis were tested for the presence of antibodies to IgA. Six class specific anti IgA antibodies and four anti IgA antibodies of limited specificity were detected. Three of these had the specificity anti alpha2 and one anti A2m(2). The 34 IgA deficient donors detected provide a source of IgA deficient blood for transfusion to patients with anti IgA antibodies.     

Genetic profiles of killer-cell immunoglobulin-like receptors and HLA ligands in Thai blood donors

Killer-cell immunoglobulin-like receptors (KIRs) play an important role in natural killer (NK) cell regulation. Interaction of KIRs with human leukocyte antigen (HLA) class I molecules can transmit signals to regulate the function of NK cells. In this study, the diversities of KIR genes and their ligands in 500 Thai blood donors were investigated. The coexistence of inhibitory KIRs (iKIR), activating KIRs (aKIR) and their ligands in the same individuals were also analyzed. Overall, 36 KIR genotypes were identified. The most common genotype was genotype AA1 (40.8%). All individuals carried at least one iKIR-HLA pair whereas 18% of the individuals lacked aKIR-HLA pair. The most common compound KIR-HLA profile was the presence of 3 iKIR-HLA pairs with 1 aKIR-HLA pair (21.4%). The most common compound gene profile of KIR-HLA pairs was the combined presence of KIR2DL3-C1, 3DL1-Bw4, 3DL2-A3/A11 and the full length KIR2DS4-its ligands (8%). This study provided a comprehensive analysis of the KIR-HLA profiles in Thai blood donors in regards to KIR genotypes, HLA ligands, KIR-HLA ligand pairs and compound gene profiles of both iKIRs and aKIRs and their ligands. These findings will be useful as baseline information for further studies in the associations of KIR genes and various diseases.     

HLA and Chinese IgA nephropathy in Taiwan

No HLA-A, B, C, DR, DQ association was found in 80 Chinese IgA nephropathy patients. In addition, no prognostic genetic marker was discovered. The subgroup of those with gross hematuria was immunogenetically distinct from the subgroup of those without gross hematuria.