ME and CFS Medical Abnormalities – HLA Types


Following is a list of articles about HLA genetic types associated with ME and CFS.

Links to the more than 1,000 peer-reviewed journal articles are listed on the ME and CFS Medical Abnormalities page of this website.


Spitzer AR, Broadman M. A retrospective review of the sleep characteristics in patients with chronic fatigue syndrome and fibromyalgia. Pain Pract. 2010 Jul-Aug;10(4):294-300.PMID: 20230458

HLA DQB1*0602 was obtained in 74 patients, and positive in 32 (43%), P < 0.0001. In patients with CFS and fibromyalgia, researchers found a sleep disorder characterized by objective hypersomnia. Seventy-three (80%) were on an abnormal multiple sleep latency testing (MSLT). Some patients had characteristics of narcolepsy. Highly fragmented sleep was seen.


Carlo-Stella N, Bozzini S, De Silvestri A, Sbarsi I, Pizzochero C, Lorusso L, Martinetti M, Cuccia M. Molecular study of receptor for advanced glycation endproduct gene promoter and identification of specific HLA haplotypes possibly involved in chronic fatigue syndrome. Int J Immunopathol Pharmacol. 2009 Jul-Sep;22(3):745-54. PMID: 19822091

Certain HLA DRB genetic types (related to the acquired immune system) are more associated with CFS than are others.


Ortega-Hernandez OD, Cuccia M, Bozzini S, Bassi N, Moscavitch S, Diaz-Gallo LM, Blank M, Agmon-Levin N, Shoenfeld Y. Autoantibodies, polymorphisms in the serotonin pathway, and human leukocyte antigen class II alleles in chronic fatigue syndrome: are they associated with age at onset and specific symptoms? Ann N Y Acad Sci. 2009 Sep;1173:589-99. PMID: 19758204

HLA DRB genetic types are related to symptom presentation and age of onset in CFS.


Smith J, Fritz EL, Kerr JR, Cleare AJ, Wessely S, Mattey DL. Association of chronic fatigue syndrome with human leucocyte antigen class II alleles. J Clin Pathol. 2005 Aug;58(8):860-3. PMID: 16049290

Forty nine patients with CFS were genotyped for the HLA-DRB1, HLA-DQA1, and HLA-DQB1 alleles and the frequency of these alleles was compared with a control group comprising 102 normal individuals from the UK.  Analysis by 2 x 2 contingency tables revealed an increased frequency of HLA-DQA1*01 alleles in patients with CFS (51.0% v 35%; odds ratio (OR), 1.93; p = 0.008). HLA-DQB1*06 was also increased in the patients with CFS (30.2% v 20.0%; OR, 1.73, p = 0.052). Only the association between HLA-DQA1*01 and CFS was significant in logistic regression models containing HLA-DQA1*01 and HLA-DRQB1*06, and this was independent of HLA-DRB1 alleles. There was a decreased expression of HLA-DRB1*11 in CFS, although this association disappeared after correction for multiple comparisons. CFS may be associated with HLA-DQA1*01, although a role for other genes in linkage disequilibrium cannot be ruled out.


Underhill JA, Mahalingam M, Peakman M, Wessely S. Lack of association between HLA genotype and chronic fatigue syndrome. Eur J Immunogenet. 2001 Jun;28(3):425-8. PMID:11422420

Fifty-eight patients were phenotyped for HLA A and B by microcytotoxicity and genotyped for HLA DRB, DQB and DPB by PCR oligoprobing, and the frequencies of antigens so assigned were compared with those from a control group of 134. No significant differences in HLA frequencies were found between patient and control groups.


Itoh Y, Igarashi T, Tatsuma N, Imai T, Yoshida J, Tsuchiya M, Murakami M, Fukunaga Y. Immunogenetic background of patients with autoimmune fatigue syndrome. Autoimmunity. 2000 Oct;32(3):193-7. PMID: 11092699

We hypothesized that if autoimmune mechanisms did play an important role in the pathogenesis of AIFS, it is possible that it is immunogenetically regulated as observed in other autoimmune disorders. In order to examine the immunogenetic background of AIFS patients, HLA-A, -B, -C, and -DR loci were analyzed serologically in 61 AIFS patients. AIFS was found to be positively associated with the class I antigen HLA-B61 and with the class II antigen HLA-DR9, with odds ratios of 2.77 (p = 0.015, Pcorr = 0.48) and 2.60 (p= 0.012, Pcorr = 0.17), respectively. A negative association was also found between AIFS and HLA-DR2 with odds ratio of 0.25 (p = 0.029, Pcorr = 0.041). When comparing anti-Sa positive AIFS patients with healthy controls, the odds ratios associated with HLA-B61, DR9, and DR2 were 3.42 (p = 0.021, Pcorr = 0.22), 3.96 (p = 0.0011, Pcorr = 0.015), and 0.16 (p = 0.0022, Porr = 0.031), respectively. Thus, the HLA associations observed in this study suggested that immunogenetic background might play a role in AIFS.


Hassan IS, Bannister BA, Akbar A, Weir W, Bofill M. A study of the immunology of the chronic fatigue syndrome: correlation of immunologic parameters to health dysfunction. Clin Immunol Immunopathol. 1998 Apr;87(1):60-7. PMID: 9576011

CFS patients had significantly increased mean fluorescence intensity readings of HLA-DR in CD4 and CD8 cells (P < 0.05). Expression of the costimulatory receptor CD28 in CD8 cells was significantly reduced, and the apoptosis repressor ratio of bcl-2/bax in both CD4 and CD8 was increased in patients (P < 0.05). Patients with increased HLA-DR expression had significantly lower SF-36 total scores, worse body pains, and poorer general health perception and physical functioning scores. Increased spontaneous lymphocyte proliferation was associated with poor general health perception.


Keller RH, Lane JL, Klimas N, Reiter WM, Fletcher MA, van Riel F, Morgan R. Association between HLA class II antigens and the chronic fatigue immune dysfunction syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S154-6. PMID: 8148444


Middleton D, Savage DA, Smith DG. No association of HLA class II antigens in chronic fatigue syndrome. Dis Markers. 1991 Jan-Feb;9(1):47-9. PMID: 1683826


van Greure CH, Bouic PJ. Aberrant in vitro HLA-DR expression in patients with chronic fatigue. S Afr Med J. 1990 Aug 18;78(4):219-20. PMID: 2382182


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