HLA-B8,DR3 haplotype affects lymphocyte blood levels.
The number of lymphocytes in the blood is constant, pointing to an effective control of circulating lymphocyte values. The mechanisms of this regulation are uncertain, although it is likely that the number of blood lymphocytes is conditioned by hormones, homing factors and cytokines whose production is at least partly restrained by genetic factors. Particularly genetic factors linked to major histocompatibility complex (MHC) appear to be involved. In human beings a decreased number of blood lymphocytes has been described in healthy subjects carrying the Human Leucocyte Antigens (HLA) haplotype HLA-B8,DR3. In the present study, to inquire into the mechanisms of this lymphocyte decreased number, we have performed an analysis of blood subset values in these subjects. When the absolute values of lymphocytes were analysed according to HLA phenotype, HLA-B8,DR3 positive subjects (N = 26) displayed significantly lower values as compared to HLA-B8,DR3 negative ones (N = 282). The analysis of lymphocyte subpopulations performed by flow cytometry in 72 subjects did not show significant changes in lymphocyte subset percentages between HLA-B8,DR3 positive subjects and negative ones. Thus, the decrease of circulating lymphocytes seems to be due to a reduction of cell number affecting all lymphocyte subsets rather than a single cell subpopulation. The analysis of in vitro spontaneous apoptosis performed by flow cytometry in a smaller sample of subjects showed a significant increase of spontaneous apoptosis in lymphocytes from HLA-B8,DR3 positive individuals suggesting a possible explanation for the deviation from normal lymphocyte count observed in these subjects. However it is intriguing that a decreased number of blood lymphocytes can be observed in healthy HLA-B8,DR3 positive subjects but also in autoimmune diseases linked to this haplotype like systemic lupus erythematosus and insulin-dependent diabetes. Furthermore, in our opinion, this finding is to be kept in mind in evaluating hematological parameters in healthy subjects.
Caruso
C
C
Servizio di Tipizzazione Tissutate, Università di Palermo, Italy.
Bongiardina
C
C
Candore
G
G
Cigna
D
D
Romano
G C
GC
Colucci
A T
AT
Di Lorenzo
G
G
Gervasi
F
F
Manno
M
M
Potestio
M
M
Tantillo
G
G
D000328:Adult; D000368:Aged; D017209:Apoptosis; D005260:Female; D015795:HLA-B8 Antigen / Q000097:blood*; D015803:HLA-DR3 Antigen / Q000097:blood*; D006239:Haplotypes; D006801:Humans; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology*; D008297:Male; D008875:Middle Aged
D015795:HLA-B8 Antigen; D015803:HLA-DR3 Antigen