An increased HLA DR2 frequency is seen in aplastic anemia patients

Abstract

The underlying etiology of aplastic anemia is unknown in the majority of patients, although medications, chemical exposure, or viral infections can be implicated in some. Genetic susceptibility to a variety of diseases has been shown and it has recently been suggested that aplastic anemia is more common in individuals who are HLA DR2+ than in the general population. To examine this question, we retrospectively analyzed the results of HLA-DR typing in 75 aplastic anemia patients who received antithymocyte globulin (ATG) therapy or an HLA-matched sibling bone marrow transplant at UCLA between 1978 and 1989. Thirty-one patients were DR2+, a 1.9-fold higher incidence than the expected number of 16.6 patients (P <.0005). Of the 37 patients who received ATG, 33 were evaluable for a response; 14 patients had either a complete (4 patients) or partial (10 patients) response, for an overall response rate of 42.4%. Of the 14 DR2+ patients who received ATG, 7 responded, for a 50% response rate, which is not significantly higher than the response rate for the DR2- patients (7 of 19 [36.8%]; P = .50). The median survival of patients who are DR2+ was slightly, but not significantly, longer than that of the DR2- patients in the ATG group (P = .19). Although the incidence of HLA DR2 was clearly increased in these patients with aplastic anemia, response rates to ATG were not significantly different in the DR2+ and DR2- patients.

Response to immunosuppressive therapy and an HLA‐DRB1 allele in patients with aplastic anaemia: HLA‐DRB1*1501 does not predict response to antithymocyte globulin

“…The present analysis on AA patients treated with ATG revealed that HLA-DRB1*1501 did not predict a favourable response to ATG therapy. This result from Japanese patients of a single ethnic origin was consistent with that of a previous report on a smaller number of patients of multiethnic origins (Nimer et al, 1994). Thus, these data suggest that identifying HLA-DRB1*1501 in a patient with AA does not predict response to ATG therapy regardless of race.…”

“…We recently have found that among several HLA class II haplotypes that determine the presentation of HLA-DR2, only a haplotype of DRB1*1501-DQA1*0102-DQB1*0602 is closely associated with a good response to CyA therapy in Japanese patients with AA (Nakao et al, 1994). On the other hand, a recent report from the United States failed to observe a higher likelihood of responding to ATG in patients with HLA-DR2 than in those without HLA-DR2 despite the fact that most individuals with HLA-DR2 in this country share the DRB1*1501-DQA1*0102-DQB1*0602 haplotype (Nimer et al, 1994;Imanishi et al, 1992). The inability to find a correlation between the specific HLA-DR serotype and a high response rate to ATG may be due to a difference in the mechanisms of action between CyA and ATG, or in the ethnic background between AA patients in the United States and Japan.…”

“…In patients with AA, an increased frequency of HLA-DR2 has been reported by several groups (Chapuis et al, 1986;Nimer et al, 1994). If possessing HLA-DR2 is associated with an immune aetiology of AA, AA patients with this HLA-DR serotype may be more likely to respond to immunosuppressive therapy than those without HLA-DR2.…”

Study of the association between cytochromes P450 2D6 and 2E1 genotypes and the risk of drug and chemical induced idiosyncratic aplastic anaemia

“…There have been no previous studies which looked for a potential genetic predisposition to drug/chemical‐induced idiosyncratic AA, apart from studies of HLA tissue typing. An increased frequency of HLA‐DR2 among AA patients has been demonstrated in two large studies (Chapuis et al , 1986; Nimer et al , 1994). A Japanese study has shown that HLA‐DRB1 subtypes of HLA‐DR2 (DRB1 1501, DRB1 1502 and DRB1 1602) occur more frequently in AA patients than in the general Japanese population (Nakao et al , 1996).…”

Analysis of T‐cell clonality in bone marrow of patients with acquired aplastic anaemia

“…anti-lymphocyte globulin (ALG)/anti-thymocyte globulin (ATG) and cyclosporin A (Young & Barrett, 1995;Frickhofen et al, 1991). An increased percentage of CD8 HLA-DR T cells in PB and BM has been found (Zoumbos et al, 1985;Maciejewski et al, 1994) as well as a significant association of AA with the HLA-DR2 allele (Nimer et al, 1994;Nakao et al, 1994). The association of an HLA-allele with autoimmune disease predisposition is one of the most clearly established factors, and is related to the MHC-restricted T-cell response (Theofilopoulos, 1995).…”