Circulating levels of insulin-like growth factor-I (IGF-I) correlate with disease status in leprosy

<p>Abstract</p> <p>Background</p> <p>Caused by <it>Mycobacterium leprae </it>(ML), leprosy presents a strong immune-inflammatory component, whose status dictates both the clinical form of the disease and the occurrence of reactional episodes. Evidence has shown that, during the immune-inflammatory response to infection, the growth hormone/insulin-like growth factor-I (GH/IGF-I) plays a prominent regulatory role. However, in leprosy, little, if anything, is known about the interaction between the immune and neuroendocrine systems.</p> <p>Methods</p> <p>In the present retrospective study, we measured the serum levels of IGF-I and IGBP-3, its major binding protein. These measurements were taken at diagnosis in nonreactional borderline tuberculoid (NR BT), borderline lepromatous (NR BL), and lepromatous (NR LL) leprosy patients in addition to healthy controls (HC). LL and BL patients who developed reaction during the course of the disease were also included in the study. The serum levels of IGF-I, IGFBP-3 and tumor necrosis factor-alpha (TNF-α) were evaluated at diagnosis and during development of reversal (RR) or erythema nodosum leprosum (ENL) reaction by the solid phase, enzyme-labeled, chemiluminescent-immunometric method.</p> <p>Results</p> <p>The circulating IGF-I/IGFBP-3 levels showed significant differences according to disease status and occurrence of reactional episodes. At the time of leprosy diagnosis, significantly lower levels of circulating IGF-I/IGFBP-3 were found in NR BL and NR LL patients in contrast to NR BT patients and HCs. However, after treatment, serum IGF-I levels in BL/LL patients returned to normal. Notably, the levels of circulating IGF-I at diagnosis were low in 75% of patients who did not undergo ENL during treatment (NR LL patients) in opposition to the normal levels observed in those who suffered ENL during treatment (R LL patients). Nonetheless, during ENL episodes, the levels observed in RLL sera tended to decrease, attaining similar levels to those found in NR LL patients. Interestingly, IGF-I behaved contrary to what was observed during RR episodes in R BL patients.</p> <p>Conclusions</p> <p>Our data revealed important alterations in the IGF system in relation to the status of the host immune-inflammatory response to ML while at the same time pointing to the circulating IGF-I/IGFBP-3 levels as possible predictive biomarkers for ENL in LL patients at diagnosis.</p

Auto-anticorpos anti-insulina em parentes em primeiro grau de diabeticos tipo I

BV UNIFESP: Teses e dissertaçõe

INSULIN AUTOANTIBODIES IN 1ST DEGREE RELATIVES OF TYPE-I DIABETIC-PATIENTS

1. Insulin autoantibodies (IAA) of first-degree relatives of type I diabetic patients and recent-onset type I diabetics were measured by radioimmunoassay. A cut-off of 60 nU/ml was established on the basis of the values of normal control individuals. The intra-assay coefficient of variation was 9.2% for a moderately positive serum (1908 +/- 176 nU/ml (mean +/- SD), N = 7; range, 1708 to 2158 nU/ml). The interassay coefficient of variation was 23.8% for a negative (normal control) serum (28.1 +/- 6.7 nU/ml, N = 6; range, 22 to 39 nU/ml) and 14.5% in a highly positive serum (6185 +/- 899 nU/ml, N = 7; range, 5053 to 7009 nU/ml).2. Insulin autoantibody levels (mean +/- SEM) were 19.3 +/- 2.8 nU/ml (range, -19 to 40 nU/ml) in 25 controls, 24.8 +/- 3.4 nU/ml (range, -17 to 59 nU/ml) in 41 type II diabetic patients, 18.5 +/- 2.4 nU/ml (range, -58 to 268 nU/ml) in 171 first-degree relatives of type I diabetic patients and 208.9 +/- 87.0 nU/ml (range, 10 to 1101 nU/ml) in 16 recent-onset type I diabetic patients. IAA levels were significantly higher in the last group compared with the other groups (P < 0.01).3. None of the controls or type II diabetics exceeded the upper limit of normality. In contrast, 9 of 171 (5.3%) first-degree relatives and 9 of 16 (56.0%) recent-onset type I diabetic patients had IAA levels above the 60 nU/ml cut-off point.4. These data indicate that this method is effective for the detection of individuals who are at high risk to develop type I diabetes.ESCOLA PAULISTA MED SCH,DEPT MED,DISCIPLINA ENDOCRINOL,RUA BOTUCATU 740,CAIXA POSTAL 20266,BR-04034 SAO PAULO,BRAZILESCOLA PAULISTA MED SCH,DEPT MED,DISCIPLINA ENDOCRINOL,RUA BOTUCATU 740,CAIXA POSTAL 20266,BR-04034 SAO PAULO,BRAZILWeb of Scienc