Expression Levels of B Cell Receptor (BCR) Signaling Pathway Factors are Associated with Conversion from Clinically Isolated Syndrome to Multiple Sclerosis

Abstract

Objective: We have previously shown altered blood B cells in the first attack blood samples of clinically isolated syndrome (CIS) pa-tients, who converted to multiple sclerosis (MS). Our aim was to investigate levels of B cell receptor (BCR)-associated genes expres-sion in converting CIS (CIS-c) and non-converting CIS patients (CIS-nc) with a 5-year follow-up.

Methods: Seven CIS-c patients, 12 CIS-nc patients and 10 age-sex matched healthy donors were enrolled in this study. RNA was extracted from frozen peripheral blood cells of subjects that were obtained in the first attack using a RNA isolation kit. Expression levels of B-cell adaptor protein with ankyrin repeats 1 (BANK1), B lymphocyte kinase (BLK) and Fc receptor-like protein 2 (FCRL2) genes were evaluated samples by real-time polymerase chain re-action (RT-PCR).

Results: CIS-nc patients showed elevated BANK1, BLK and FCRL2 gene expression levels as compared to CIS-c patients and healthy controls.

Conclusions: Expression levels of the genes that inhibit BCR signal-ing are increased in CIS-nc, suggesting that inhibiting exaggerated B cell response by optimization of B cell proliferation may prevent the progression of clinically isolated syndrome to MS.

Keywords

• Clinically isolated syndrome
• multiple sclerosis
• B cell receptor
• BANK1
• BLK
• FCRL2

B Hücre Reseptör (BHR) Sinyal Yolağı Faktörlerinin Ekspresyon Düzeyleri Klinik İzole Sendromdan Multipl Skleroza Dönüşümle İlişkilidir

Abstract

Amaç: Daha önceki çalışmalarımızda, multipl skleroza (MS) dö-nüşen klinik izole sendrom (KİS) olgularının ilk atakta alınan kan örneklerinde periferik kan B hücre düzeylerinin değiştiğini göste-rilmiştir. Bu çalışmada beş yıllık takipte MS’e dönüşen ve dönüşme-yen KİS olgularında B hücre reseptör (BHR) ilişkili genlerin ekspres-yon düzeylerinin araştırılması amaçlanmıştır.

Yöntem: Yedi MS’e dönüşen, 12 MS’e dönüşmeyen KİS olgusu ile yaş ve cinsiyet açısından eşleştirilmiş 10 sağlıklı donör çalışmaya dahil edildi. İlk atak döneminde elde edilen donmuş periferik kan mononükleer hücrelerinden (PKMH) RNA izolasyon kiti kullanılarak total RNAlar izole edildi. Örneklerden gerçek zamanlı polimeraz zincir reaksiyonu (RT-PCR) yöntemi ile ankrin tekrarlı B-hücre adap-tör proteini (BANK1), B lenfosit kinaz (BLK), Fc reseptör benzeri pro-tein 2 (FCRL2) genlerinin ekspresyonları değerlendirildi.

Bulgular: MS’e dönüşmeyen KİS olgularında BANK1, BLK ve FCRL2 gen ekspresyon düzeyleri MS’e dönüşen KİS olguları ve sağlıklı kontrollere kıyasla artmış olarak saptandı.

Sonuç: BHR sinyalizasyonunu inhibe eden gen ekspresyonlarının MS’e dönüşmeyen olgularda artması, abartılı B hücre yanıtının B hücre proliferasyonunun optimize edilmesi yoluyla baskılanması-nın KİS’ten MS’e ilerleyişi engelleyebileceğini düşündürmüştür.

Keywords

• Klinik izole sendrom
• multipl skleroz
• B hücre reseptörü
• BANK1
• BLK
• FCRL2

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