Cytotoxic T-lymphocyte antigen-4 (CTLA-4) exon 1 polymorphism affects lymphocyte profiles in bronchoalveolar lavage of patients with sarcoidosis.
BACKGROUND
Sarcoidosis is a systemic disease characterized by T-cell activation and subsequent granuloma formation at the site of involvement. Genetic susceptibility is a key factor in the pathogenesis of this disease, and genes involved in T-cell regulation are potential candidates. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a negative regulator of T-cell activation expressed on activated T-cells. The G allele of the CTLA-4 exon 1 polymorphism has previously been described to be associated with disease susceptibility in several autoimmune diseases. We investigated the relationship of CTLA-4 to disease susceptibility and cell profiles in bronchoalveolar lavage (BAL) in Japanese sarcoidosis patients.


METHODS
Japanese sarcoidosis patients (n = 135) and controls (n = 97) were typed for an A/G bi-allelic polymorphism in exon 1 of CTLA-4 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the distribution of genotypes was compared between both groups. Sixty-seven patients underwent BAL, and cell profiles in BAL fluid were compared between patients with G/G genotype and those with A/A genotype.


RESULTS
No significant differences in the distribution of genotype and allele frequencies were found between sarcoidosis (GG: 46%, AG: 39%, AA: 15%) and controls (GG: 42%, AG: 49%, AA: 8%). Patients with G/G genotype had significantly increased lymphocyte ratios, lymphocyte counts, and CD4(+) cell counts in BAL fluid compared with patients with A/A genotype (p < 0.05).


CONCLUSIONS
CTLA-4 exonl polymorphism might affect BAL fluid lymphocyte profiles in Japanese sarcoidosis patients.
Handa
Tomohiro
T
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan. hanta@kuhp.kyoto-u.ac.jp
Nagai
Sonoko
S
Ito
Isao
I
Shigematsu
Michio
M
Hamada
Kunio
K
Kitaichi
Masanori
M
Izumi
Takateru
T
Mishima
Michiaki
M
D000328:Adult; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D001992:Bronchoalveolar Lavage Fluid; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007141:Immunoglobulin Fc Fragments; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012507:Sarcoidosis / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D007141:Immunoglobulin Fc Fragments