Novel inflammatory biomarkers and their correlation to Chlamydia pneumoniae titres in acute ischemic stroke

Abstract

Background: Young stroke patients constitute 15%-30% of all stroke patients in India as against 3.0%-8.5% reported from the West. The mechanisms for stroke in the young may include unconventional risk factors such as infections. We aimed to investigate the role (if any) of Chlamydia pneumoniae antibodies in young patients with acute ischemic stroke (AIS). Several proinflammatory cytokines and biomarkers are released early after the onset of brain ischemia. We assessed the role of heat shock protein (hsp) 65, neopterin, and myeloperoxidase upregulation after AIS in predicting stroke severity. We also assessed relationship of upregulated inflammatory biomarkers with C pneumoniae antibody titres (IgG, IgA, and IgM).

Methods: Eighty acute stroke patients and healthy age- and sex-matched controls were recruited. Blood samples were drawn within 1 week from the onset of stroke. Detection of IgA, IgG, and IgM antibodies to C pneumoniae was done with a validated microimmunofluorescence technique from 5 mL of serum in all subjects. Inflammatory biomarkers such as neopterin, myeloperoxidase and hsp 65 were estimated with sandwich enzyme linked immunosorbent assay (ELISA) method.

Results: hsp 65 and neopterin were significantly elevated in all stroke patients with respect to healthy controls (odds ratio [OR], 4.9; 95% confidence interval [CI], 23.5-67.8; P = .001 and OR, 4.4; 95% CI, 2.08-9.4; P = .04, respectively). Eighty-one percent of cases were seropositive for IgA versus 32% of controls (P = .003), and IgG was positive in 52.7% versus 17.3% of controls (P = .05). Myeloperoxidase levels were similar in patients and controls. Correlation and multiple regression indicated a high level of predictability and sensitivity of hsp 65 to IgA. C. pneumoniae antibody titres when all other variables were constant (F [4,90] = -6.8, P = .001). Patients with high NIHSS scores (>15) had elevated levels of hsp 65 (mean, 13.2 ng/mL) suggesting correlation with stroke severity.

Conclusions: The study demonstrated high levels of hsp 65 and neopterin levels in AIS correlated to significantly elevated IgA titres of C pneumoniae. Elevated levels of hsp 65 were associated with stroke severity.

Keywords: Acute ischemia; C pneumoniae; inflammatory biomarkers; stroke severity.