Association of Anti-β 1 and Anti-M2 Antibodies with Autonomic Nervous System Modulation in Patients with Chronic Chagas Cardiomyopathy

Abstract Background: Different immune mechanisms of myocardial damage involved in the pathophysiology of Chagas disease coexist with high titers of autoantibodies induced by T. cruzi . There are few studies in the literature about the adaptive role of anti-β1 and anti-M2 antibodies in chronic Chagas cardiomyopathy (CCC). Objectives: To evaluate the association between anti-β1 and anti-M2 antibodies with heart rate variability (HRV) parameters on 24h Holter monitoring and the rate-pressure product (RPP) on cardiopulmonary exercise testing (CPET). Methods: Anti-β1 and anti-M2 antibody titers were measured by enzyme-linked immunosorbent assay (ELISA) in 64 patients affected by CCC. Analysis of HRV was performed through the time-domain indices NNs, mean NN, SDNN, SDANN, SDNN index, NNNs, RMSSD, and pNN50. Spearman's correlation coefficient was used to assess the association between antibody titers and numerical variables. The Mann-Whitney test was used for comparison between two groups. Multiple linear regression was used to identify independent variables capable of explaining anti-β1 and anti-M2 antibody titers at the 5% significance level. Results: On 24h Holter, during the period of greatest parasympathetic activation (2:00-6:00 a.m.), an inverse association was found between anti-β1 titers and SDNN (rs=-0.13, p =0.041, n=43), as well as a direct association between anti-M2 titers and SDANN ( r s=0.317, p =0.039, n=43). Regarding CPET variables, anti-β1 titers were directly associated with RPP (rs=0.371, p =0.005, n=56). The subgroup of patients with a normal chronotropic response showed higher anti-β1 titers than the subgroup with an impaired response (p=0.023). RPP was an independent explanatory variable for anti-β1 titers, although with a low coefficient of determination (R2=0.147). Conclusion: The findings of this study suggest that, in patients with CCC, anti-β1 and anti-M2 antibodies may affect HRV parameters. RPP was directly associated with higher anti-β1 titers.

Polymorphisms of PPARgamma2 gene in patients with type 2 diabetes mellitus and obesity / 대한내과학회지

BACKGROUND: Peroxisome proliferator activated receptor-gamma (PPAR-gamma) is a nuclear receptor that regulate adipocyte differentiation and modulate intracellular insulin-signaling events. As such, PPARgamma is a candidate gene for several human disorders including obesity and type 2 diabetes mellitus. The objective of our study was to examine the relationship between genetic variation of PPARgamma2 and diabetes and obesity in Korean subjects. METHODS: We studied 99 subjects with type 2 diabetes mellitus, 128 obesity patients and 97 controls. Screening for mutation at codon 12 and 115 of PPARgamma2 were carried out by PCR-RFLP analyses. Statistical significance was evaluated by Chi-square test. RESULTS: The allele frequency of the Pro12Ala PPARgamma2 variant were 0.05 in controls, 0.06 in type 2 diabetes group, and 0.07 in obesity group (p=0.47). Pro115Gln variant were only proline homozygote in all groups. Genotype frequencies were also similar and conformed to expectations of the Hardy-Weinberg rule. The presence of PPARgamma2 gene variant was no associated with concentrations of total cholesterol, triglyceride, HDL-cholesterol, and also with fasting glucose. CONCLUSION: We concluded that the Pro12Ala and Pro115Gln PPARgamma2 missense mutation may not be associated with type 2 diabetes mellitus and obesity in Korean patients.

A case of conventional antimitochondrial antibody test-negative primary biliary cirrhosis / 대한내과학회지

Primary biliary cirrhosis is a chronic progressive cholestatic liver disease of unknown cause that usually affects middle-aged women and eventually leads to cirrhosis and liver failure. It is characterized by the progressive destruction of small intrahepatic bile ducts, portal inflammation, and progressive scarring. The diagnosis is made by these characteristic pathologic findings and the presence of antimitochondrial antibody. Immunofluorescence, the most widely used method for determining antimitochondrial antibody, is less sensitive and specific than ELISA or immunoblotting and influenced by observer interpretation. Therefore, it is important to detect anti-M2 antibody, the most specific antibody of primary biliary cirrhosis, by ELISA or immunoblotting when antimitochondrial antibody is not detected by immunofluorescence method which can lead to the incorrect diagnosis as autoimmune cholangitis. We describe a case of primary biliary cirrhosis with antimitochondrial antibody negative by immunofluorescence, anti-M2 antibody positive by ELISA. We confirmed primary biliary cirrhosis by liver biopsy.