The relationship between HLA-B*51 subtypes, clinical manifestations and severity of Behçet's syndrome: a large Italian cohort study

Pietro Leccese; Maria Carmela Padula; Eustachio Vincenzo Santospirito; Rosa Colucci; Nancy Lascaro; Angela Anna Padula; Salvatore D'Angelo

doi:10.1093/rap/rkad087

The relationship between HLA-B*51 subtypes, clinical manifestations and severity of Behçet's syndrome: a large Italian cohort study

Rheumatol Adv Pract. 2023 Oct 17;7(3):rkad087. doi: 10.1093/rap/rkad087. eCollection 2023.

Authors

Pietro Leccese¹, Maria Carmela Padula¹, Eustachio Vincenzo Santospirito², Rosa Colucci², Nancy Lascaro¹, Angela Anna Padula¹, Salvatore D'Angelo¹

Affiliations

¹ Rheumatology Institute of Lucania (IReL) and Rheumatology Department of Lucania, San Carlo Hospital of Potenza, Potenza, Italy.
² Tissue Typing Laboratory C.R.T. Basilicata, Madonna delle Grazie Hospital, Matera, Italy.

Abstract

Objectives: Behçet's syndrome (BS) is a chronic multisystemic inflammatory disorder of unclear aetiology. The predominant BS susceptibility locus was identified within HLA-B*51. HLA-B*51 subtypes were previously studied as disease susceptibility markers. Few data are now available about the relationship between B*51 subtypes and clinical phenotype. The aim of this study was to genotype HLA-B*51 subtypes in a series of Italian BS patients and to test the association with clinical manifestations and disease severity (Krause's index).

Methods: HLA-B*51 subtype genotyping for 63 alleles (B*51:01-B*51:63) was performed by PCR after DNA extraction from whole blood of BS patients. The correlation of disease clinical manifestations and severity (Krause's index) with the HLA-B*51 allele and its subtypes was analysed.

Results: We enrolled 241 (140 male and 101 female) BS patients, and HLA-B*51 frequency was 62.7% (151 of 241). One hundred and eight of the HLA-B*51-positive patients carried the B*51:01 subtype (108 of 151, 71.5%), 39 of 151 (25.8%) the B*51:08 subtype, 2 of 151 (1.3%) the B*51:02 subtype, 1 of 151 (0.7%) the B*51:05 subtype, and 1 of 151 (0.7%) the B*51:07 subtype. We found that ocular involvement was statistically associated with HLA-B*51 positivity and with B*51:01 and B*51:08 subtypes (P < 0.05). We also found that disease severity was higher in HLA-B*51-positive patients than in negative patients, but without statistical significance (median Krause's index 5.1 vs 4.1, P > 0.05).

Conclusion: Here, we confirm a high frequency of the HLA-B*51 allele in our group of BS patients. B*51:01 and B*51:08 were found to be the most common subtypes, and an association of both subtypes with ocular involvement was also underlined.

Keywords: Behçet’s syndrome; HLA-B*51; genotyping; subtypes.