Class-specific anti-IgA Antibodies Research Articles

強力化学療法と同種骨髄移植療法が施行し得たｌｇＡ欠損症を伴う急性骨髄性白血病の１症例

Deficiency of IgA with circulating class-specific anti-IgA antibodies is one of the major causes of anaphylactic reaction in transfusion medicine. This problem is more serious in the management of patients with hematological malignancies or other types of bone marrow failure. Here we report a case of acute myeloid leukemia with IgA deficiency who underwent intensive chemotherapy and allogeneic bone marrow transplantation. To avoid the production of anti-IgA antibody, platelet concentrates were collected from donors who were IgA-deficient. Additional support with platelets and RBC components from donors who had circulating IgA was provided using products washed and replaced with 0.9% normal saline. Complete remission was achieved after a single course of remission induction therapy. After one course of consolidation chemotherapy, allogeneic bone marrow transplantation from an HLA-matched sibling was performed. No anaphylactic reaction was observed after any transfusion. No circulating anti-IgA antibodies were detectable after the full recovery of hematopoiesis in this patient. These findings indicate that allogeneic blood component products collected from donors with IgA deficiency are useful in myeloablative therapy in patients with hematological disorders. By washing with normal saline, products from donors with normal IgA levels are also acceptable. Further studies to elucidate the clinical usefulness of precise genomic and expressional analysis of IgA gene are required to ensure the safety of transfusion medicine in patients with IgA deficiency. Furthermore, the establishment of blood bank registry systems for IgA-deficient blood donors is important to the maintenance of a stable supply of blood components for IgA-deficient patients who require transfusion therapy.

Clinical Manifestations in Selective IgA Deficiency in Childhood; A Follow‐up Report

Clinical manifestations in 40 children with selective IgA deficiency were studied during a follow-up period of 2-10 years. The patients were divided into two groups: group I consisted of 25 children with "sporadic" IgA deficiency and group II of 15 children with "familial" IgA deficiency. Respiratory tract infections including otitis media were frequent in both groups. Concomitant IgG2-IgG4 deficiency was found in two patients in group I. Longitudinal serum IgG levels were elevated significantly in both groups. Atopic complaints were observed in 10 children of the "sporadic" group, but only in two of the "familial" group. However, elevated serum IgE levels were more often found in group II. Two children of group I were mentally retarded and chromosomal examination showed abnormalities in both. Anti-IgA antibodies were detected in one child in group I and three children in group II. These three patients had an IgA deficient mother with class-specific anti-IgA antibodies. Concomitant IgG4-IgE deficiency was found in all four.

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

Sera from 22 phenytoin-treated epileptic patients with a serum IgA<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.

Familial selective IgA deficiency with circulating anti-IgA antibodies: A distinct group of patients?

Two families were investigated in which the mothers had selective IgA deficiency and circulating class-specific anti-IgA antibodies. Both gave birth to two children who were found to be IgA deficient. Three of these children developed anti-IgA antibodies before puberty. In vitro immunoglobulin production studies performed in the children of both families revealed an IgA B cell defect combined with IgA-specific excessive T suppressor function in all four. The mechanisms by which transplacental passage of maternal anti-IgA antibodies could have interfered with the developing IgA system in the offspring are discussed.

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).

IgG anti-IgA1 and anti-IgA2 antibodies: their measurement by an enzyme-linked immunosorbent assay and their relationship to disease.

IgG anti-IgA antibodies were measured by an enzyme-linked immunosorbent assay using one IgA1 and one IgA2 (m1) myeloma and a pooled IgA protein preparation as antigens. Class-specific anti-IgA antibodies occurred in 0.8% of non-IgA-deficient sera and 24.3% of IgA-deficient sera. Antibodies reacting with IgA1 only occurred in 2.6% of non-IgA-deficient sera and 6.7% of IgA-deficient sera. Antibodies reacting with IgA2 only occurred in 0.6% of non-IgA-deficient sera and 2.7% of IgA-deficient sera. The prevalence of anti-IgA in IgA deficients with inflammatory disease was higher (81.8%) than in IgA deficients without disease (24.1%) and was accounted for by class-specific antibodies.

Anti-IgA antibodies in pregnancy.

A survey of 28,000 pregnant women revealed an incidence of IgA deficiency (serum IgA less than 1 mg per deciliter) of 1 in 450, which is identical to that in a normal blood-donor population of both sexes. Using an enzyme-linked immunosorbent assay (ELISA) in a study of 61 serum samples from IgA-deficient pregnant women, we observed antibodies to IgA2 alone in 20 per cent, as compared with 7.5 per cent of pregnant women not deficient in IgA and no IgA-deficient blood donors. Antibodies reacting with IgA1 alone were present in occasional serum samples (2 to 7 per cent) from all groups studied, and class-specific anti-IgA antibodies were present in 17 per cent of IgA-deficient blood donors and in 16 per cent of IgA-deficient pregnant women. Blocking experiments showed that some serum samples contained an antibody that reacted with both IgA1 and IgA2, whereas others contained two antibodies, one reacting with IgA1 and the other with IgA2. The anti-IgA2 antibodies tended to diminish in titer after delivery. The ELISA was, as expected, more sensitive than the hemagglutination assay. The offspring of IgA-deficient mothers (but not of IgA-deficient fathers) had levels of serum IgA below the normal mean (21 of 27); 12 had levels more than 1 S.D., and seven had levels more than 2 S.D., below the normal mean. Of the seven infants with serum IgA levels more than 2 S.D. below the normal age-related mean, five had mothers with anti-IgA antibodies during gestation. It is possible that maternal anti-IgA exerts a transplacental effect on the fetal immune system, causing IgA deficiency in some instances.

Human antibodies to immunoglobulin A (IgA). a radioimmunological method for differentiation between anti-IgA antibodies and IgA in the serum of IgA deficient individuals

In the sera of 12 out of 27 individuals with IgA deficiency (serum level below 0.02 mg IgA/ml) class-specific anti-IgA antibodies were demonstrated by haemagglutination. These sera showed false-positive results in a solid-phase inhibition radioimmunoassay (RIST) (apparent IgA concentration between 0.6 and 13.7 μg IgA/ml) indicating that the RIST is not an appropriate test for the analysis of serum of IgA deficient individuals. A modification of the RIST is proposed (titration RIA) that permits differentiation between low levels of IgA and class-specific anti-IgA antibodies. With this test IgA deficient individuals could be classified as those with low but detectable levels of IgA and those with class-specific anti-IgA antibodies. A computer procedure was developed to calculate both the amount and the avidity (K) of the anti-IgA antibodies and to simulate the assay system. The K value calculated from experimental points proved to be an overestimation of the K value which fitted most adequately in the simulation. The comparison of the results with clinical findings indicated a possible correlation between the amount and the avidity of the anti-IgA anti-bodies and the appearance of anaphylactic reactions after transfusion of IgA.

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.