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Allele and haplotype frequency at human leucocyte antigen class I/II and immunomodulatory cytokine loci in patients with myelodysplasia and acute myeloid leukaemia: in search of an autoimmune aetiology
Author(s) -
Gowans Duncan,
O'Sullivan Alan,
Rollinson Sara,
Roddam Phillipa,
Groves Mike,
Fegan Chris,
Morgan Gareth,
Bowen David
Publication year - 2002
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2002.03452.x
Subject(s) - immunology , haplotype , human leukocyte antigen , myelodysplastic syndromes , allele , allele frequency , medicine , myeloid , biology , antigen , genetics , gene , bone marrow
Summary. An autoimmune mechanism in the␣pathogenesis of myelodysplastic syndrome (MDS) is suggested by response to immunosuppression, with CD8 + T‐lymphocytes implicated in the haematopoietic suppression. We therefore sought evidence for human leucocyte antigen (HLA) restriction and variant frequency differences in selected polymorphisms at␣the loci for the immunomodulatory cytokines, tumour necrosis factor α (TNF‐α), lymphotoxin‐α (LT‐α) and interleukin 10 (IL‐10) in patients with MDS and acute myeloid leukaemia (AML) compared with normal controls. DNA from 150 MDS/AML patients [24 AML, 53 refractory anaemia (RA), 25 RA with excess blasts (RAEB), four RAEB in transformation (RAEBt), 21 sideroblastic leukaemia, 22 chronic myelomonocytic leukaemia] was screened. Control data was from Scottish blood donors (HLA class I/II), healthy General Practitioner‐based subjects (TNF‐α/LT‐α) and published values (IL‐10). HLA class I/II haplotypes were determined using sequence‐specific primers. Polymorphisms were assayed at TNF‐α−308, LT‐α +252 and IL10 −824, −597 and −1082 loci. Variant frequencies of common haplotypes at HLA class I and II, high‐/low‐producer TNF‐α/LT‐α and IL‐10 loci were not different between patients and controls or within the French–American–British, International Prognostic Scoring System or cytogenetic subgroups and were not associated with altered survival for MDS/AML patients. TNF2 allele frequency was greater in the MDS/AML cohort (χ 2 = 6·593, P < 0·05) but the biological significance was uncertain in the absence of an increased high‐producer TNF‐α/LT‐α haplotype frequency. We can find no genetic influence for these polymorphisms in HLA class I/II, TNF‐α/LT‐α and IL‐10 loci on either predisposition or disease progression in MDS/AML.