Relationship of CTLA4 and CD28 polymorphisms with lung involvement, HRCT findings and pulmonary function tests in Turkish patients with ankylosing spondylitis

Clin Respir J. 2017 Sep;11(5):593-601. doi: 10.1111/crj.12388. Epub 2015 Oct 9.

Abstract

Background and aims: Ankylosing spondylitis (AS) is a multisystem disorder with ocular, pulmonary, and cardiovascular involvement. The incidence of pulmonary involvement varies from 1 to 52%. Abnormal T-cell function-derived immune responses are involved in AS pathogenesis. Numerous genes such as CTLA4 and CD28 control T-cell functions. In this study, we aimed to address the relationship between CTLA4 and CD28 polymorphisms and lung involvement in Turkish patients with AS.

Methods: A cross-sectional evaluation of 80 healthy and 89 AS subjects with no active infection or malignancy was performed to determine the relationship between pulmonary involvement and CTLA4 and CD28 gene polymorphisms. All patients were assessed for clinical, radiological, and spirometric findings. Descriptive statistics, chi-square tests, and independent-sample t-tests were used for statistical analyses.

Results: All patients with the CD28 CC genotype (n = 4) had abnormal HRCT, but it was not significant (p = 0.47). All of the normal HRCT patients have CD 28 T alleles. In addition to this data ; 4 patients who have not any T alleles have abnormal HRCT finding. It was significant and was considered that T genotype have protective effect (p= 0,047) on radiologic involvement but no other association was found between CTLA4 and CD28 gene polymorphism with respect to pulmonary function tests (PFT), diffusion capacity, and clinical characteristics in the Turkish patients with AS.

Conclusion: Our results suggest a possible association of CTLA4 and CD28 variants with AS pulmonary involvement. Furthermore, these results may lead to the development of new therapeutic agents to control more aggressive forms of the disease. However, further studies are needed in larger populations.

Keywords: Ankylosing spondylitis - CD28 - CTLA4 - lung involvement.

MeSH terms

  • Adult
  • Alleles
  • CD28 Antigens / genetics*
  • CTLA-4 Antigen / genetics*
  • Cross-Sectional Studies
  • Female
  • Humans
  • Incidence
  • Lung Diseases / diagnostic imaging*
  • Lung Diseases / epidemiology
  • Lung Diseases / pathology
  • Lung Diseases / physiopathology*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Respiratory Function Tests / methods*
  • Spondylitis, Ankylosing / complications*
  • Spondylitis, Ankylosing / epidemiology
  • Spondylitis, Ankylosing / genetics*
  • Spondylitis, Ankylosing / immunology
  • Tomography, X-Ray Computed / methods*
  • Turkey / epidemiology
  • Young Adult

Substances

  • CD28 Antigens
  • CTLA-4 Antigen
  • CTLA4 protein, human