Mathews Christine E, Brown Eric L, Martinez Perla J, Bagaria Upasana, Nahm Moon H, Burton Robert L, Fisher-Hoch Susan P, McCormick Joseph B, Mirza Shaper
Division of Epidemiology, Human Genetics, and Environmental Health, University of Texas Health Science Center, School of Public Health, Brownsville Regional Campus, Brownsville, TX, USA.
Clin Vaccine Immunol. 2012 Sep;19(9):1360-9. doi: 10.1128/CVI.00268-12. Epub 2012 Jul 3.
The goal of the study was to determine baseline protective titers of antibodies to Streptococcus pneumoniae surface protein A (PspA) and capsular polysaccharide in individuals with and individuals without type 2 diabetes mellitus. A total of 561 individuals (131 individuals with diabetes and 491 without) were screened for antibodies to PspA using a standard enzyme-linked immunosorbent assay (ELISA). A subset of participants with antibodies to PspA were retested using a WHO ELISA to determine titers of antibodies to capsular polysaccharide (CPS) (serotypes 4, 6B, 9V, 14, 18C, 19A, 19F, and 23F). Functional activity of antibodies was measured by assessing their ability to enhance complement (C3) deposition on pneumococci and promote killing of opsonized pneumococci. Titers of antibodies to protein antigens (PspA) were significantly lower in individuals with diabetes than controls without diabetes (P = 0.01), and antibodies showed a significantly reduced complement deposition ability (P = 0.02). Both antibody titers and complement deposition were negatively associated with hyperglycemia. Conversely, titers of antibodies to capsular polysaccharides were either comparable between the two groups or were significantly higher in individuals with diabetes, as was observed for CPS 14 (P = 0.05). The plasma specimens from individuals with diabetes also demonstrated a higher opsonophagocytic index against CPS serotype 14. Although we demonstrate comparable protective titers of antibodies to CPS in individuals with and individuals without diabetes, those with diabetes had lower PspA titers and poor opsonic activity strongly associated with hyperglycemia. These results suggest a link between diabetes and impairment of antibody response.
该研究的目的是确定2型糖尿病患者和非2型糖尿病患者中抗肺炎链球菌表面蛋白A(PspA)和荚膜多糖抗体的基线保护滴度。使用标准酶联免疫吸附测定(ELISA)对总共561名个体(131名糖尿病患者和491名非糖尿病患者)进行PspA抗体筛查。对一部分有PspA抗体的参与者使用世界卫生组织ELISA进行复测,以确定抗荚膜多糖(CPS)(血清型4、6B、9V、14、18C、19A、19F和23F)的抗体滴度。通过评估抗体增强补体(C3)在肺炎球菌上沉积以及促进调理吞噬的肺炎球菌杀伤的能力来测量抗体的功能活性。糖尿病患者中针对蛋白抗原(PspA)的抗体滴度显著低于无糖尿病的对照组(P = 0.01),并且抗体的补体沉积能力显著降低(P = 0.02)。抗体滴度和补体沉积均与高血糖呈负相关。相反,两组之间针对荚膜多糖的抗体滴度相当,或者在糖尿病患者中显著更高,如CPS 14所观察到的(P = 0.05)。糖尿病患者的血浆样本对CPS血清型14也表现出更高的调理吞噬指数。尽管我们证明糖尿病患者和非糖尿病患者中针对CPS的抗体保护滴度相当,但糖尿病患者的PspA滴度较低且调理活性较差,这与高血糖密切相关。这些结果表明糖尿病与抗体反应受损之间存在联系。