Serum ghrelin and obestatin levels in HIV-infected patients: Effect of 36 weeks of antiretroviral treatment / Niveles séricos de Ghrelina y Obestatina en pacientes infectados con VIH: efecto de 36 semanas de tratamiento antirretroviral

Introduction: Patients with HIV+ often present lipid disturbances. The role of ghrelin and obestatin in these lipid disturbances is not clear. The effect of antiretroviral (ART) drugs on those molecules is also unknown. This study measured ghrelin and obestatin levels, as well as metabolic markers, in patients with HIV+ before and after 36 weeks of ART. Material and methods: Twenty HIV-positive, ART-naïve patients who started a scheme consisting of tenofovir/emtricitabine+lopinavir/ritonavir were enrolled. Plasma samples were collected before and after 36 weeks of treatment. Serum ghrelin and obestatin levels were quantitated by ELISA; glucose, cholesterol, and triglyceride levels were measured by colorimetric and enzymatic methods, and cardiovascular risk was calculated by the atherogenic index of plasma (AIP). Results: All patients completed 36 weeks of ART. Total cholesterol (p<0.001), LDL-C (p=0.019), HDL-C (p=0.003), VLDL-C (p=0.002), and triglyceride levels (p=0.021) significantly increased after treatment. AIP revealed increased cardiovascular risk at baseline, which remained high after treatment. There was a statistically significant increase in obestatin level in the unpaired and paired analyses, while ghrelin levels only showed a trend to increase. Changes in ghrelin and obestatin levels positively correlated, but no correlation was seen with any metabolic parameter. Conclusion: After 36 weeks of ART, patients showed an altered lipid profile, but there were no significant changes in cardiovascular risk. Ghrelin and obestatin levels increased after 36 weeks of ART, but the increase was only significant for obestatin. Changes in ghrelin and obestatin positively correlate

Introducción: Los pacientes con VIH+ frecuentemente presentan alteraciones del perfil lípidico. El papel de ghrelina y obestatina en estas complicaciones no está claro. El efecto del tratamiento antirretroviral (TAR) en dichas moléculas es desconocido. Este estudio determinó los niveles de ghrelina y obestatina, así como los parámetros metabólicos en pacientes VIH+ antes y después de 36 semanas del TAR. Material y métodos: Participaron 20 pacientes VIH+, vírgenes a TAR, que iniciaron con un esquema de tenofovir/emtricitabina + lopinavir/ritonavir. Se tomaron muestras de plasma antes y después de 36 semanas de tratamiento. Los niveles séricos de ghrelina y obestatina fueron cuantificados por ELISA, los parámetros bioquímicos fueron determinados por métodos colorimétricos, se evaluó el riesgo cardiovascular por medio del índice aterogénico del plasma (AIP). Resultados: Los pacientes completaron 36 semanas del TAR. Los niveles de colesterol total (p<0,001), c-LDL (p=0,019), c-HDL (p=0,003), c-VLDL (p=0,002) y triglicéridos (p=0,021) mostraron un incremento estadísticamente significativo posterior al tratamiento. El AIP reveló un riesgo cardiovascular alto. Los niveles de obestatina se incrementaron significativamente en el análisis pareado y no pareado; y ghrelina solo mostró tendencia al incremento. Los cambios en ghrelina y obestatina correlacionaron positivamente, sin embargo no correlacionaron con los parámetros metabólicos. Conclusión: Los pacientes VIH+ mostraron un perfil lipídico alterado después de 36 semanas del TAR. Los niveles de ghrelina y obestatina se incrementaron tras 36 semanas del TAR. El riesgo cardiovascular es persistente. Los cambios en ghrelina y obestatina mostraron una correlación positiva

Serum ghrelin and obestatin levels in HIV-infected patients: Effect of 36 weeks of antiretroviral treatment.

INTRODUCTION: Patients with HIV+ often present lipid disturbances. The role of ghrelin and obestatin in these lipid disturbances is not clear. The effect of antiretroviral (ART) drugs on those molecules is also unknown. This study measured ghrelin and obestatin levels, as well as metabolic markers, in patients with HIV+ before and after 36 weeks of ART. MATERIAL AND METHODS: Twenty HIV-positive, ART-naïve patients who started a scheme consisting of tenofovir/emtricitabine+lopinavir/ritonavir were enrolled. Plasma samples were collected before and after 36 weeks of treatment. Serum ghrelin and obestatin levels were quantitated by ELISA; glucose, cholesterol, and triglyceride levels were measured by colorimetric and enzymatic methods, and cardiovascular risk was calculated by the atherogenic index of plasma (AIP). RESULTS: All patients completed 36 weeks of ART. Total cholesterol (p<0.001), LDL-C (p=0.019), HDL-C (p=0.003), VLDL-C (p=0.002), and triglyceride levels (p=0.021) significantly increased after treatment. AIP revealed increased cardiovascular risk at baseline, which remained high after treatment. There was a statistically significant increase in obestatin level in the unpaired and paired analyses, while ghrelin levels only showed a trend to increase. Changes in ghrelin and obestatin levels positively correlated, but no correlation was seen with any metabolic parameter. CONCLUSION: After 36 weeks of ART, patients showed an altered lipid profile, but there were no significant changes in cardiovascular risk. Ghrelin and obestatin levels increased after 36 weeks of ART, but the increase was only significant for obestatin. Changes in ghrelin and obestatin positively correlate.

PTPN22 1858C>T polymorphism is associated with increased CD154 expression and higher CD4+ T cells percentage in rheumatoid arthritis patients.

BACKGROUND: CD40 is a costimulatory molecule for B cells, and CD154 is a marker of CD4+ T cells activation. CD40-CD154 interaction promotes pro-inflammatory cytokines secretion and autoantibodies production. PTPN22 gene encodes LYP protein, an inhibitor of T- and B-cell activation. PTPN22 1858C>T polymorphism confers rheumatoid arthritis (RA) susceptibility. Hence, we evaluate the relationship between 1858C>T polymorphism with CD40 and CD154 expression and IFN-γ secretion in RA patients. METHODS: PTPN22 1858C>T polymorphism was genotyped in 315 RA patients and 315 control subjects (CS) using PCR-RFLP method. Later, we selected only ten anti-CCP-positive RA patients, naïve to disease-modifying antirheumatic drugs and ten CS, all with known 1858C>T PTPN22 genotype. The CD40 and CD154 membrane expressions were determined by flow cytometry in peripheral B and T cells, correspondingly. RESULTS: The B cells percentage and mCD40 expression were similar between RA and CS (P > 0.05) and we did not find an association between these variables and the 1858C>T polymorphism. The CD4+ T cells percentage was higher in RA patients than CS (P = 0.003), and in the RA group, the CD4+ T cells percentage and mCD154 expression were higher in the 1858 T allele carriers (P = 0.008 and P = 0.032, respectively). The IFN-γ levels were lower in RA patients carrying the PTPN22 risk allele (P = 0.032). CONCLUSION: The PTPN22 1858 T risk allele is associated with increased CD4+ T cells percentage and high mCD154 expression in RA patients, which could favor the pro-inflammatory cytokine release and the establishment of the inflammatory response at the seropositive RA.

Clinical and immunological aspects of anti-peptidylarginine deiminase type 4 (anti-PAD4) autoantibodies in rheumatoid arthritis.

Rheumatoid arthritis (RA) is the most common rheumatic autoimmune disease worldwide, which causes progressive joint damage and can lead to functional disability. Despite prominent advances in RA diagnosis and treatment during the last 20years, there is still a need for novel biomarkers that aid in diagnosis and prognosis of this heterogeneous disease. Citrullination is a key post-translational modification implicated on anti-citrullinated protein/peptide antibodies (ACPA) production in RA, catalyzed by human peptidylarginine deiminases (PADs). Among these enzymes, PAD4 has been recognized as an important player in RA pathogenesis and the enzyme itself is a target of autoantibodies (anti-PAD4) in a subgroup of RA patients. Accumulating evidence suggests that anti-PAD4 autoantibodies may be useful as a severity biomarker in RA and recent studies have also shed light on the functional significance of these autoantibodies. This review summarizes the evidence on anti-PAD4 autoantibodies in RA, and addresses its usefulness for disease diagnosis and prognosis. Novel immunological aspects of anti-PAD4 antibodies and their relevance to RA pathogenesis are also discussed.

Increased CD28 serum levels are not associated with specific clinical activity in systemic lupus erythematosus.

CD28 is one of the main activator receptors involved in systemic lupus erythematosus (SLE) pathogenesis, and its expression and serum levels are significantly higher in patients with SLE and other autoimmune diseases than in healthy controls (HC). However, it is unknown whether this increase is associated with specific organ damage. Therefore, our objective was to measure the CD28 levels in serum from SLE and HC groups to confirm the CD28 serum levels increase, as reported previously, and to determine whether this increase was associated with specific organ activity and the SLE Disease Activity Index (SLEDAI). Forty SLE patients and 40 matched HC were included, and the age, disease duration, SLEDAI and Mexican SLEDAI were recorded for the SLE group. CD28 serum levels were measured by ELISA. There was a statistically significant increase in the CD28 serum levels of SLE patients compared to controls (p = 0.039); however, we did not find any significant correlation with disease activity indices or organ involvement, although we found a significant but low correlation with C3. Our results and a review of the literature suggest that the increase in CD28 serum levels may be the result of CD28 gene overexpression, which could be related to the decrease in CD28+ T cells, T-cell hyporesponsiveness and immune impairment that occurs in SLE.