Human leukocyte antigen genes may outweigh racial background when generating a specific immune response in sarcoidosis

Abstract

Presented is a sarcoidosis patient of African origin, who was adopted at an early age and grew up in Sweden.This patient displayed an immune response identical to that previously reported in human leukocyte antigen (HLA)-DR17 positive Caucasian sarcoidosis patients in Scandinavia, with T-cell receptor AV2S3+ T-cells accumulating in the lungs. HLA typing also established that she was DR17 positive, which is a rare HLA type for individuals of African origin.To the authors' knowledge, this specific immune response has not previously been reported in patients of African origin. Moreover, the clinical manifestations of sarcoidosis were similar to those known to be strongly linked to HLA-DR17 in Scandinavians,i.e.with Löfgren's syndrome.The case presented here suggests certain human leukocyte antigen genes to be strongly linked to specific immune responses that are identical irrespective of the racial background. If such an immune response were important for the subsequent clinical manifestations, this case would argue for the importance of human leukocyte antigen genes in the genetic predisposition to sarcoidosis.

Review: Role of Genetics in Susceptibility and Outcome of Sarcoidosis

“…Several reports of the very strong association between HLA-DRB1*03 and lungaccumulated CD4þ T cells expressing the TCR AV2 gene segment support the hypothesis of specific antigen presentation in sarcoidosis. [39][40][41]57,66,67 Further support of this notion is the finding that Swedish sarcoidosis patients expressing HLA-DRB3*01, which has similar antigen peptide binding capacities as DRB1*0301, also have lung accumulated TCR AV2S3 positive T cells (Fig. 1).…”

“…An African-born individual who was adopted by Swedish parents and grew up in Sweden, and was DRB1*0301 positive, was thus found to develop classical LS, including the characteristic local immune response in these patients with lung-accumulated T cells expressing TCR AV2S3. 57 In the ACCESS study on a total of 736 U.S. patients, only one of the 393 white patients and four of the 325 African American patients, respectively, were classified as LS. 58 Moreover, 472 of the patients were HLA typed, and DRB1*0301 was expressed by 14% of white and 5% of African American patients.…”

HLA-DRB1*1101: A Significant Risk Factor for Sarcoidosis in Blacks and Whites

“…Nevertheless, the majority of HLA class II alleles that are associated with sarcoidosis may be similar in both blacks and whites, and the increased frequency of sarcoidosis in blacks could be due to the different distribution of HLA alleles in blacks compared to that in whites. Similarly, Grunewald and Eklund (Grunewald and Eklund 2001) recently reported a case of sarcoidosis in an African that had an HLA type (DR 17) that has been associated with a specific immunological profile (i.e., increased lung T cells that express the AV2S3 T cell receptor) and clinical presentation, Lofgren syndrome, that is frequently seen in Scandinavians and is unusual in Africans.…”

CD4+T cells in sarcoidosis: targets and tools

“…In certain other ethnic groups, such as Japanese, HLA-DRB1*0301 is extremely rare and accordingly there is usually no accumulation of AV2S3 + BAL T cells in the lungs of these patients [62]. However, among HLA-DRB1*0301-positive non-Caucasian patients, AV2S3 + T cells do accumulate in BAL fluid, showing the importance for the HLA-DRB1*0301 gene in generating this local immune response [63]. Environmental factors are also important, as demonstrated by the finding of a pair of HLA-DRB1*0301-positive monozygotic twins, of whom one had sarcoidosis and also lung-accumulated AV2S3 + T cells at disease onset, but not after clinical recovery.…”