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Giant cell arteritis (GCA) and Takayasu’s arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/ MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P = 7.54E-07; ORGCA = 1.19, ORTAK = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA = 5.52E-04, ORGCA = 1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus.

Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P = 7.54E-07; ORGCA = 1.19, ORTAK = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA = 5.52E-04, ORGCA = 1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus., This work was supported by SAF2012– 34435 from the Spanish Ministry of Economy and Competitiveness, BIO-1395 from Junta de Andalucía, and RD12/0009/0004 from the RETICS Program (RIER) of Instituto de Salud Carlos III (ISCIII). FDC was recipient of a grant from the ‘Ramón y Cajal’ programme of the Spanish Ministry of Economy and Competitiveness (RYC-2014–16458). MCC and JHR are supported by Ministerio de Economía y Competitividad (SAF 14/57708R), cofunded by “Fondo Europeo de Desarrollo Regional, Unión Europea, Una manera de hacer Europa” [Instituto de Salud Carlos III and Fondo Europeo de desarrollo regional (FEDER) (PIE 13/00033)]. The Vasculitis Clinical Research Consortium has received support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54AR057319), the National Center for Research Resources (U54 RR019497), the Office of Rare Diseases Research, and the National Center for Advancing Translational Science. The VCRC is part of the Rare Diseases Clinical Research Network (RDCRN).

DOI: 10.26650/IUITFD.426162Amaç: Romatoid Artrit (RA), nedenibilinmeyen, esas olarak periferik eklemleri progresif olarak tutan kronikmultisistemik bir hastalıktır. Hümoral ve hücresel immün yanıtları arasında birbağ olan, IgG‘ nin Fc reseptörleri otoimün hastalıkların etyoloji vepatogenezinde oldukça ilgi çekmektedir. Geniş genetik varyasyon sergileyen bubölge Romatoid artrit de dahil olmak üzere çeşitli kronik inflamatuvarhastalıklara yatkınlık ile ilişkilidir. Bu çalışmasında Romatoid Artrit‘ teFcγRIIIA V158F gen polimorfizminin sıklığının araştırılması ve hasta klinik velaboratuar bulgularıyla karşılastırılması amaçlanmıştır.Gereç ve Yöntem: Çukurova Üniversitesi TıpFakültesi Romatoloji Bilim Dalı polikliniğine Nisan 2010-Haziran 2011 tarihleriarasında başvuran ve Amerikan Romatizma Derneği‘ nin tanı kriterlerine göre RAtanısı almış 105 RA‘lı hasta ve 110 sağlıklı kontrol çalışmaya dahil edildi.Hasta ve kontrollerden öyküsünde diyabet, tiroid fonksiyon bozuklukları,geçirilmiş veya mevcut kalp hastalıkları, malignite, nörolojik hastalıklar ilekronik inflamatvuar hastalıklardan bir ya da daha fazlası olanlar çalışma dışıbırakıldı. RA‘ lı hastaların hastalıkla ilgili semptomları, sistemik hastalıkvarlığı, ilaç kullanımı, hastalık süreleri ve aile öyküsü sorgulandı. Tümolgulara genel fizik muayene ve romatolojik muayeneleri yapıldı ve rutinlaboratuvar tetkikleri ile CRP, RF, ESR, ANA, Anti-DNA düzeyleri istendi. Hastagrubu ARA‘nın fonksiyonel sınıflandırması kullanılarak evrelere ayrıldı. Alınankan örneklerinde real time PCR yöntemi ile FcγRIIIA V158F gen polimorfizmleriaraştırıldı.Bulgular: Hasta ve kontrol grubunun Fc γRIIIA gen polimorfizm dağılımları arasında anlamlı fark saptanmadı (p=0,106).Hastaların tanı aldıkları yaş dağılımları ile gen polimorfizmi arasında anlamlıfark saptanmadı (p=0,919). Hastaların cinsiyet dağılımlarına göre de genpolimorfizmi açısından anlamlı fark saptanmadı (p=0,552). Hastalığın klinikbulgularından olan akciğer ve göz tutulumları, romatoid nodül varlığı ile genpolimorfizmi arasında ilişki saptanmadı. RF ve ANA sonuçları ile genpolimorfizmi arasında da anlamlı fark saptanmadı (p=0,625, p=0,716). Hastalarınanti-CCP sonuçları ile gen polimorfizmi arasında anlamlı fark saptanmadı(p=0,136). Sonuç: Çalışmamızda RA patogenezi ile Fc γRIIIA 158 gen polimorfizmi arasında anlamlı bir ilişki saptanmamıştır., DOI: 10.26650/IUITFD.426162Objective: Rheumatoid Arthritis (RA) is achronic multisystem disease with unknown etiology that progressively affectsperipheral joints. Receptors, which serve as links between humoral and cellularimmune responses, recognize the Fc region of immunoglobulin G (FcR) and havebecome the focus of many research studies concerning the etiology andpathogenesis of autoimmune diseases. This region displays extensive geneticvariation, which has been associated with susceptibility to various chronicinflammatory disorders including RA. This study aimed to investigate thefrequency of the FcγRIIIA V158F genetic polymorphism and compare clinical andlaboratory findings in RA.Materials and Methods: Between April 2010and June 2011, 105 patients, who had been diagnosed with RA according to theAmerican Rheumatology Association (ARA) diagnostic criteria, were admitted tothe Cukurova University Department of Rheumatology outpatient clinic and 110healthy controls were included in this study. Patient groups were divided intostages using the ARA functional classification. The FcγRIIIA V158F gene polymorphismof patients was investigated from blood samples using the real-time PolymeraseChain Reaction (PCR) method.Results: There was no significantdifference in the distribution of the FcγRIIIA polymorphism between patientsand controls (p=.106). There were no significant differences between thedistribution of age at diagnosis of patients with the gene polymorphism(p=.919) or in the gene polymorphism (p=.552). No association was found betweenthe gene polymorphism and clinical signs of disease such as eye involvement andthe presence of rheumatoid nodules. There was also no significant associationbetween the gene polymorphism with rheumatoid factor, anticyclic citrullinatedpeptide, and antinuclear antibodies (p=.625, p=.136, p=.716, respectively).Conclusion: In our study, no significantrelationship was found between the FcγRIIIA V158F gene polymorphism and thepathogenesis of RA.

Amaç: Kompleman aktivasyonunun lektinyolağında rol oynayan ve doğal immün sistemin bir parçası olan mannoz bağlayıcılektin (MBL), çeşitli patojenlerin mannan gruplarının uyarısı ile aktive olur.MBL genindeki bazı polimorfizmler (örn. kodon 52, kodon 54 polimorfizmleri)MBL’nin serum düzeylerinde değişikliklere yol açarak, infeksiyon hastalıklarınayatkınlığa neden olabildiği gibi, bazı otoimmün ve inflamatuvar hastalıklarınpatogenezine de katkıda bulunabilir. Bu çalışmada, ailesel Akdeniz ateşi (AAA)hastalarında MBL geni kodon 52 ve kodon 54 polimorfizmlerinin sıklığını vebaşta sekonder amiloidoz olmak üzere, hastalığın klinik özellikleri ile olasıilişkilerini araştırmayı amaçladık.Gereç ve Yöntem: Yüzelli-yedi AAAhastasında ve hastalarla akrabalık ilişkisi olmayan benzer demografikdağılımdaki 150 sağlıklı kontrolde MBL genindeki R52C C>T ve G54D G>Apolimorfizmleri sekanslama yöntemi ile araştırıldı. AAA hastalarının MEFV genianalizleri, klinik özellikleri ve ataksız dönemdeki serum CRP düzeylerikaydedildi. Genetik sonuçlar ile klinik ve laboratuvar bulgular arasındakiolası ilişkiler incelendi.Bulgular: MBL geni R52C C>T polimorfizmihastaların %12,7’sinde, kontrol grubunun %10,6’sında saptandı. G54D G>Apolimorfizmi hastaların %26,8’sinde, kontrollerin %26,7’sinde saptandı.Polimorfizm sıklığı açısından, iki grup arasında anlamlı fark bulunamadı(p=0,79 ve 0,98). İncelenen MBL geni polimorfizmleri ile hastaların çeşitliklinik özellikleri (ör. amiloidoz, ateş, kolşisin yanıtı, MEFV mutasyonları)arasında anlamlı ilişki bulunamadı. AAA hastalarının ortalama CRP değeri4,90±6,72 mg/dL olup, ataksız dönemde serum CRP düzeyi normalden yüksek(>0,8 mg/dL) olan hastalarda MBL kodon 52 polimorfizmi sıklığı %25,2, kodon54 polimorfizmi sıklığı %14,8 oranında bulundu. AAA hastalarında yüksek CRPdüzeyine göre kodon 52 ve kodon 54 polimorfizmi sıklıkları farklı bulunmadı(p=0,399). AAA hastalarında M694V mutasyonu ile amiloidoz arasında (p=0,002) veM694I mutasyonu ile kolşisin direnci arasında (p=0,016) anlamlı ilişkisaptandı.Sonuç: AAA hastaların ataksız dönemdeki CRPdüzeyleri ve taşıdıkları klinik özellikler ile MBL polimorfizmleri arasındaanlamlı ilişki bulunamaması, AAA hastalarının proinflamatuvar durumda olduğunuve MBL aracılı mekanizmaların bu süreçlere katkısının olmadığınıdüşündürmektedir. Olgularımızda M694I ile kolşisin direnci arasında anlamlıilişki saptanmış olması dikkate değer bir bulgudur. Yine olgularımızda M694Vile amiloidoz arasında anlamlı ilişki bulunması önceki literatür bulguları ileuyumludur ve M694V’nin hastalık şiddeti ve prognozu için önemli olduğu görüşünüdesteklemektedir., Objective: Mannose-binding lectin (MBL),which takes part in the lectin pathway of the complement system as a componentof innate immunity, is activated by the stimulation of various bacteriallectins. It is known that some of the MBL gene polymorphisms (eg, codon 52,codon 54) that may lead to alterations in MBL serum levels are responsible forthe susceptibility to infectious diseases and contribute to the pathogenesis ofvarious autoimmune and inflammatory diseases. In this study, we planned toinvestigate the frequencies of codon 52 and codon 54 polymorphisms of the MBLgene in FMF patients and their association with the clinical features of thedisease.Materials and Methods: MBL genepolymorphisms of the R52C C>T and G54D G>A were investigated bysequencing in 157 FMF patients and 150 unrelated healthy controls. MEFV genemutations in FMF patients were investigated by sequencing method. The clinicalcharacteristics of the patients and the C-reactive protein (CRP) values inattack-free phase were recorded. Statistical analysis of the findings wasperformed with the SPSS version 18.0.Results: The MBL gene R52C C>Tpolymorphism was detected in 12.7% of the patients and 10.6% of the controls.G54D G>A polymorphism was detected in 26.7% of the patients and 26.6% of the controls. There was no significantdifference between the two groups (p=0.794). No significant correlationsbetween MBL gene polymorphisms and various clinical characteristics of patients(amyloidosis, fever, colchicine response) were found. Mean CRP level of the FMFpatients was 4.90±6.72 mg/dL. In FMF patients with elevated serum CRP levels(>0.8 mg/L), codon 54 MBL polymorphism frequency was 14.8%, codon 52polymorphism frequency was 25.2%. Codon52 and codon 54 polymorphism frequencies were not different between the groupsaccording to CRP level (p>0.05). In FMF patients, significant correlationswere found between M694V and amyloidosis (p=0.002) as well as between M694I andcolchicine resistance (p=0.016).Conclusion: The absence of a relationshipbetween MBL polymorphisms and high CRP levels in attack-free phase of FMFpatients suggests that the proinflammatory state in some FMF patients is notrelated to MBL mediated mechanisms. In our cases, the significant relationshipbetween M694I and colchicine resistance is remarkable. Our finding of thesignificant relationship between M694V and amyloidosis is consistent with previousliterature and demonstrating the importance of M694V in disease severity andprognosis.

Giant cell arteritis (GCA) and Takayasu’s arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P = 7.54E-07; ORGCA = 1.19, ORTAK = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA = 5.52E-04, ORGCA = 1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus.

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