ABNORMAL LYMPHOCYTE SUBSETS IN KUWAITI PATIENTS WITH TYPE-1 INSULIN-DEPENDENT DIABETES-MELLITUS AND THEIR FIRST-DEGREE RELATIVES

Circulating lymphocyte subset imbalance is associated with type-1 insu lin-dependent diabetes mellitus (IDDM). To examine the imbalance in th ese immunoregulatory cells in Kuwaitis with type-1 diabetes and their first-degree relatives we analysed T-lymphocyte subsets and HLA-DR exp ression (activation) in 18 IDDM patients with a family history of IDDM and 18 non-diabetic first-degree relatives of the IDDM patients. Both IDDM patients and their first-degree relatives showed a mild lymphope nia. Total T lymphocytes, CD3(+) cells, in IDDM patients and their fir st-degree relatives were reduced compared to control subjects (P < 0.0 01), Total B lymphocytes, CD19(+) cells, was increased in IDDM patient s (P = 0.001), but was comparable to controls in IDDM patients' first- degree relatives. No quantitative abnormality was demonstrated in CD4( +) cells in IDDM patients; however, these cells were higher in their f irst-degree relatives P = 0.0089), Suppressor T lymphocytes, CD8(+) ce lls, in first-degree relatives and controls were not significantly dif ferent; however, these cells were significantly reduced in IDDM patien ts (P = 0.001). The ratio of CD4(+)/CD8(+) cells was higher in IDDM pa tients and their first-degree relatives compared to controls (P = 0.00 07 and 0.0103, respectively), Activated T lymphocytes, HLA-DR(+)CD3(+) cells, were significantly increased in IDDM patients and their first- degree relatives. HLA-DR3 was the most common antigen found in IDDM pa tients (77% vs. 20% in controls, P = 0.00021). The second most common antigen was HLA-DR4 (55% vs. 24% in controls, P = 0.0566). However, no relationship was found in the levels of CD3(+), CD4(+) or CD8(+) cell s in patients possessing either DR3 or DR4. These results suggest that T-lymphocyte subset imbalance not only characterizes the cellular aut oimmunity in the pathogenesis of IDDM but may also be significant in e arly pre-diabetic stages in those with a family history of IDDM.