Alterations in lymphocyte subpopulations in type 1 (insulin-dependent) diabetes mellitus: exploration of possible mechanisms and relationships to autoimmune phenomena

Herold, Kevan C.; Huen, A H; Gould, Lacey M.; Traisman, Howard S.; Rubenstein, Arthur H.

doi:10.1007/bf00275660

Cited by 46 publications

(34 citation statements)

References 16 publications

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“…The lymphocyte ratio, despite its poor specificity, is a simple and widely used test for evaluation of the cell mediated immune response [16] and is reported to be reduced in patients with a long duration of disease [3,4]. Immunoregulatory lymphocyte subsets have a major role in the induction of a primary immune response (as in the case of the B hepatitis vaccine) and any abnormality of these cells in number and/or function may result in impaired generation of a specific cell mediated and humoral immune response.…”

Section: Discussionmentioning

confidence: 99%

“…The number of circulating helper (CD4) cells is reduced [2], the helper/suppressor (CD4/CD8) lymphocyte ratio is decreased [3,4], phagocytic activity is impaired [5] and lymphocyte blastogenesis is reduced [6]. These are amongst the most consistent alterations reported in vitro and may well account for the greater susceptibility to infection in patients with poor metabolic control [7].…”

mentioning

confidence: 99%

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Reduced protection against hepatitis B virus following vaccination in patients with Type 1 (insulin-dependent) diabetes

Pozzilli

Visalli

et al. 1987

Diabetologia

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Summary. Twenty patients with well controlled Type I (insulin-dependent) diabetes of at least 10 years duration and 47 control subjects were vaccinated against the hepatitis B virus using the Hevac B vaccine. The vaccine was administered into the deltoid region on three occasions at intervals of 1 month. Thereafter a fourth dose was given to subjects still negative for antibody to hepatitis B surface antigen (HbsAb). The median rise of HbsAb titres was 230 mlU/ml in normal subjects and 50mlU/ml in diabetic patients (p<0.001). Eight patients (40%) failed to reach HbsAb titres above 30 mlU/ml, the level considered to give optimal protection against the infection, whereas only one normal control subject failed to reach this level. Five patients (25%) showed no response despite a fourth dose of the vaccine. There was an increased frequency of HLA-DR7 in low responders and a decreased (< 1.5) helper/suppressor lymphocyte ratio. Diabetic patients are thus less likely to mount a protective antibody response following vaccination against hepatitis. Since hepatitis B surface antigen is reported to be considerably more common in diabetic patients than control subjects, infection with hepatitis B virus may have a greater risk of chronicity in diabetes.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Reduced protection against hepatitis B virus following vaccination in patients with Type 1 (insulin-dependent) diabetes

Pozzilli

Visalli

et al. 1987

Diabetologia

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“…Increased NK cell activity has been reported in the periphery of individuals with type 1 diabetes [1][2][3][4][5][6], but a role for these innate immune cells in the pathogenesis of type 1 diabetes has not, however, been elucidated. NK cells act by either activating or inhibiting cytolysis [7] and their activity is controlled by the balance of inhibitory and activating receptors on the cell surface [8].…”

Section: Introductionmentioning

confidence: 99%

An increased frequency of NK cell receptor and HLA-C group 1 combinations in early-onset type 1 diabetes

Mehers

Long

Slik³

et al. 2011

Diabetologia

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Aims/hypothesis Natural killer (NK) cells serve as primary immune surveillance and are partially regulated by combinations of killer immunoglobulin-like receptor (KIR) genes and their HLA class I ligands. Alterations in NK cell activity have been associated with type 1 diabetes. The aim of this study was to determine whether KIR-HLA class I gene frequency: (1) is altered in a current population with type 1 diabetes compared with healthy controls; and (2) has changed over the half century in which the incidence of type 1 diabetes has increased rapidly.Methods KIR-HLA class I gene frequencies were compared in 551 individuals diagnosed with type 1 diabetes ≤15 years of age (394 in a current cohort and 157 from the historical 'Golden Years' cohort) and 168 healthy controls. The overall balance of activation and inhibition was analysed using KIR-HLA genotype models. Results Children with type 1 diabetes who were positive for KIR2DS2/KIR2DL2 and KIR2DL3 were more often homozygous for HLA-C group 1 and this effect was strongest in children diagnosed with diabetes before the age of 5 years (p=0.003, corrected p [p corr ]=0.012) and (p=0.001, p corr = 0.004), respectively. Children with type 1 diabetes have fewer inhibitory KIRs with their corresponding ligands compared with healthy controls (p=1.9×10 −4 ). This pattern of NK activation has not changed significantly in individuals with type 1 diabetes over the last half century. Conclusions/interpretation Activating combinations of KIR-HLA genes are more frequent in young children with type 1 diabetes diagnosed in the first 5 years of life, suggesting that NK cell responses may be altered in this group.

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“…In the first ground-breaking studies, decreased CD4/CD8 lymphocyte ratios, reduced lymphocyte blastogenesis, and acquired defects in interleukin-2 production were observed in people affected by DM (1,2,3). Subsequent research revealed reduced T-cell primary responses to protein antigens (4).…”

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confidence: 99%

Antibody Responses to Immunizations in Children with Type I Diabetes Mellitus: a Case-Control Study

Eisenhut

Chesover

Misquith

et al. 2016

Clin Vaccine Immunol

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Type I diabetes mellitus (DM) has been associated with abnormalities of T cells. Our objective was to assess whether antibody responses to T-cell-dependent and -independent antigens in children with DM are lower than those of children without DM. We performed a case-control study matching children with DM to children without DM by age and by assessing antibody levels to pneumococcal serotypes, Haemophilus influenzae, and tetanus and diphtheria toxoids and reassessing antibody levels in patients with antibody levels below protective thresholds after booster immunization. We recruited 36 children with DM and 36 age-matched controls. The mean age was 10 years. There was no difference between groups in antibody levels against the antigens tested. Pneumococcal antibody levels below the protective threshold were found in 35.9% of DM patients after conjugate pneumococcal vaccination with no difference between groups. Booster immunization with unconjugated pneumococcal vaccine resulted in a median level against pneumococcal serotypes of 2.3 g/ml (range, 0.05 to 664.7 g/ml) in children with DM and 6.1 g/ml (0.12 to 203.36 g/ml) in children without DM (P ‫؍‬ 0.013). Over 85% of children had levels above the protective threshold after booster immunization with no difference between groups. There was no evidence for a reduced antibody response to T-cell-dependent antigens given during childhood immunizations in children with DM. There was a reduced antibody response to antigens of pneumococcal strains in children with DM given unconjugated pneumococcal polysaccharide vaccine compared to that of children without DM without being associated with a difference in percentage of antibody levels below the protective threshold between groups.T ype I diabetes mellitus (DM) has been associated with multiple abnormalities of T-cell function and quantities. In the first ground-breaking studies, decreased CD4/CD8 lymphocyte ratios, reduced lymphocyte blastogenesis, and acquired defects in interleukin-2 production were observed in people affected by DM (1, 2, 3). Subsequent research revealed reduced T-cell primary responses to protein antigens (4). Other investigations demonstrated features of a suppression of a T-helper cell 1 phenotype, with reduced expression of Th1-associated chemokine receptors and decreased secretion of Th1 cytokines (5).A previous study showed that compared to healthy controls, adult DM patients mounted a significantly impaired primary antibody response to T-cell-dependent primary protein antigens used for immunization, like hepatitis A vaccine and diphtheria toxoid, while the response to the T-cell-independent pneumococcal polysaccharide vaccine was not different. Patients with type II diabetes showed a normal response to immunization, illustrating that hyperglycemia is not involved in a change of the immune response (6).People with DM are susceptible to bacterial and particularly pneumococcal infection and are at increased risk of morbidity and mortality from bacteremia due to Streptococcus pneumoniae (7,8).Ther...

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Alterations in lymphocyte subpopulations in type 1 (insulin-dependent) diabetes mellitus: exploration of possible mechanisms and relationships to autoimmune phenomena

Cited by 46 publications

References 16 publications

Reduced protection against hepatitis B virus following vaccination in patients with Type 1 (insulin-dependent) diabetes

Reduced protection against hepatitis B virus following vaccination in patients with Type 1 (insulin-dependent) diabetes

An increased frequency of NK cell receptor and HLA-C group 1 combinations in early-onset type 1 diabetes

Antibody Responses to Immunizations in Children with Type I Diabetes Mellitus: a Case-Control Study

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