Soluble HLA-DR serum levels are associated with smoking but not with acute coronary syndrome

Abstract Background & aims Elevated soluble HLA-DR (sHLA-DR) serum levels have been reported in HLA class II-associated inflammatory disorders. We have previously shown that the HLA class II allele HLA-DRB1*01 may predispose to acute coronary syndromes (ACS). To our knowledge, sHLA-DR serum levels have not been studied in ACS. Methods sHLA-DR serum levels were measured in 477 ACS patients as cases and 475 area- and sex-matched controls by sandwich enzyme-linked immunosorbent assay. Binary logistic regression and ordinal logistic regression analyses adjusted for clinical parameters were conducted to evaluate the associations of sHLA-DR levels. Results ACS patients had lower sHLA-DR serum levels compared to controls (OR = 0.837; 95% CI = 0.704–0.994; p  = 0.043). After adjustment for smoking status, this association was no longer significant. This was explained by the notion that current smoking was inversely associated with sHLA-DR levels both in cases (OR = 0.592; 95% CI = 0.553–0.908; p  = 0.016) and in controls (OR = 0.356; 95% CI = 0.226–0.563; p  = 0.000010). A similar effect was not seen with other cardiovascular risk factors. Conclusions The results indicate, for the first time, that lower sHLA-DR levels are associated with smoking, but not with ACS. This is an important finding because previous studies of sHLA-DR have not accounted for the possible associations between smoking and sHLA-DR levels. Further studies are required to confirm these novel results and explore the mechanisms behind the observed associations.