Inflammatory cell differentiation and chemotaxis and extracellular tissue repair markers are
Inflammatory cell differentiation and chemotaxis and extracellular tissue repair markers are correlated with pulmonary dysfunction in HIV infected individuals presenting with community-acquired pneumo
University of Manitoba
Background: Prior studies have shown that HIV patients develop permanent pulmonary dysfunction following an episode of community-acquired pneumonia (CAP. It has been shown that HIV patients experience chronic inflammation despite combination antiretroviral therapy (cART). Inflammation and immune activation are thought to be the main drivers behind accelerated end organ dysfunction in HIV patients. Therefore, we hypothesized that CAP exacerbates inflammation in HIV patients resulting in an accelerated decline in lung function. Methods: A prospective cohort pilot study enrolled patients hospitalized in Medellín, Colombia. Plasma, sputum and pulmonary function test (PFT) measurements were retrieved at the time of admission and at one month follow-up. Immunoassays were performed to measure the concentration of 13 molecules involved in inflammation and extracellular matrix remodeling. The concentrations of the molecules were compared between the two groups using Wilcoxon test. Correlations between PFT values and the concentration of the molecules measured were done using Spearman's correlation. Results: Sixteen patients were eligible for the study, they were split into two groups: HIV and HIV+CAP. There were 9 patients in the HIV+CAP group and 7 patients in the HIV group. The HIV+CAP group had lower lung function compared to the HIV group. BAFF and TIMP-1 correlated negatively with FVC %predicted, (BAFF, r= -0.639, p= 0.009) and (TIMP-1, r = -0.689, p= 0.004). APRIL, BAFF and CCL3 correlated negatively with FEV1 %predicted (APRIL, r = -0.561, p= 0.026), (BAFF, correlation coefficient = -0.505, p= 0.048) and (CCL3, r = -0.55, p= 0.028). Furthermore, the concentrations of BAFF, CCL3 and TIMP-1 were statistically significant between the two groups. CCL3 and TIMP-1 were significant at admission (APRIL, 95% Confidence Interval [CI], 92.00 to 131.75, p=0.028 and TIMP-1, 95% Confidence Interval [CI], 102010.14 to 218914.86, p=0.014), BAFF was significant at one month-follow up (95% Confidence Interval [CI], 508.39 to 1077.56, p= 0.003). Conclusion: APRIL, BAFF, CCL3 and TIMP-1 have the potential to serve as biomarkers for predicting pulmonary dysfunction following CAP infection in HIV patients. Furthermore BAFF, CCL3 and TIMP-1 are involved in inflammation response in humans. We speculate that abnormal expression of these molecules may play a role in dysregulating the inflammatory response in HIV patients with CAP, which leads to pulmonary dysfunction.