HLA-DPB1 Glutamate 69: a Genetic Marker of Beryllium Disease

Abstract

Chronic beryllium disease (CBD) is a lung disorder related to beryllium exposure and is characterized by the accumulation in the lung of beryllium-specific CD4 + major histocompatibility complex (MHC) class II-restricted T lymphocytes. Evaluation of MHC class II genes in 33 CBD cases and 44 controls has shown a negative association with HLA-DPB1 * 0401 ( P < 0.001) and a positive association with HLA-DPB1 * 0201 ( P < 0.05) alleles, which differ at residues 36, 55 to 56, and 69 of the β 1 chain. Among CBD cases, 97 percent expressed the HLA-DPB1 * 0201-associated glutamic acid (unaffected population, 30 percent; P < 0.001) at residue 69, a position involved in susceptibility to autoimmune disorders. This suggests that HLA-D P has a role in conferring susceptibility and that residue 69 of HLA-DPB1 could be used in risk assessment for CBD.

Molecular Interaction and Enzymatic Activity of Macrophage Migration Inhibitory Factor with Immunorelevant Peptides

“…Its role in antigen presentation has been established for viral and bacterial antigens and in alloreactivity (57). One of the strongest HLA class II genetic associations with immunological disorders is the presence of a glutamic acid at position HLA-DP ␤69, which confers susceptibility to metal-induced disorders as chronic beryllium disease and hard metal diseases (58,59). MIF association with other HLA class II polymorphic variants cannot be excluded at the present time and will be a matter of further investigations.…”

The degree of matching at HLA-DPB1 predicts for acute graft-versus-host disease and disease relapse following haematopoietic stem cell transplantation

“…An association has been shown between certain DPB1 alleles and susceptibility to particular diseases. [13][14][15][16][17][18] HLA-DP-specific T-cells have been isolated from skin biopsies at the onset of graft-versushost-disease (GvHD) in HLA-DP mismatched transplants. 19 It has also been reported that most leukaemic blasts are accessible to direct lysis by allogeneic HLA-DPspecific T cells, suggesting that these cells may also be responsible for an antileukaemic effect.…”

Sarcoid Myositis with Anti-Ku Antibody Consistent with both Sarcoidosis and Polymyositis

“…HLA-DPB1*05:01 does not have glutamic acid at position 69, however, HLA-DPB1 *09:01 does. On the other hand, another study revealed a strong association between glutamic acid at position 69 in HLA-DPB1 and chronic beryllium disease (22). It has been suggested that HLA-DPB1 may play an important role in antigen presentation and recognition in chronic granulomatous diseases.…”