HLA-DR typing and lymphocyte subset evaluation in rheumatic heart disease: A search for immune response factors

Abstract

Several autoimmune diseases have been associated with increased frequencies of specific histocompatibility (HLA) antigens, particularly for the D (DR) locus, that may be linked to immune response genes. Rheumatic valvular heart disease (RHD) has been postulated to have autoimmune features, but HLA associations have not been established. We, therefore, performed HLA-DR typing in 33 consecutive patients with RHD and in 82 normal blood bank control subjects. We also evaluated the frequencies of lymphocyte subsets by means of monoclonal antibodies and immunofluorescence flow cytometry and made functional correlations for the natural killer cell (NKC) in patient subsets. The DR patterns in RHD were heterogeneous. However, significant differences were noted for DR4 and DR6. DR4 was present in 52% (17 of 33) of RHD patients vs 32% (26 of 82) of control subjects ( p < 0.05). DR6 was present in 6% (2 of 33) of patients vs 26% (21 of 82) of control subjects ( p < 0.02). The associated relative odds of DR4 was 2.3 and the etiologic fraction was 0.30. The relative odds of DR6 was 0.19 and the preventive fraction was 0.21. A distinct clinical profile was not associated with DR4 positivity or DR6 negativity. The frequency of lymphocyte subsets was not significantly changed except for OKT8. Median NKC numbers tended to be higher in RHD patients than in control subjects ( p < 0.05). In contrast, NKC functional activity tended to be lower in RHD; median lymphocyte to target cell (K562 line) ratio resulting in 50% killing ( L T 50 ) was 20.5 in RHD patients vs 11.5 in control subjects ( p = 0.05). In conclusion, these findings suggest that chronic RHD is not distinguishable by a consistent HLA-DR or abnormal lymphocyte subset profile; however, immune factors, either DR or lymphocyte subtype associated, may play a role in some cases of RHD and bear further investigation.