Patients with Behçet's disease (BD) suffer from episodic inflammation often affecting the orogenital mucosa, skin, and eyes. To discover new BD-susceptibility loci, we performed a genome-wide association study (GWAS) of 779,465 SNPs with imputed genotypes in 1,209 Turkish BD patients and 1,278 controls. We identified novel associations at CCR1, STAT4, and KLRC4. Additionally, two SNPs in ERAP1, encoding ERAP1 p.Asp575Asn and p.Arg725Gln, recessively conferred disease risk. These findings replicated in 1,468 independent Turkish and/or 1,352 Japanese samples (combined meta-analysis p < 2 × 10−9). We also found evidence for interaction between HLA-B*51 and ERAP1 (p = 9 × 10−4). The CCR1 and STAT4 variants were associated with gene expression differences. Three risk loci shared with ankylosing spondylitis and psoriasis (MHC-I, ERAP1, and IL23R, and the MHC-I-ERAP1 interaction), as well as two loci shared with inflammatory bowel disease (IL23R and IL10) implicate shared pathogenic pathways in the spondyloarthritides and BD.

The presence of symptom clusters, regional differences in disease expression and similarities with, for example, Crohn's disease suggest multiple pathological pathways are involved in Behçet syndrome. These features also make formulating disease criteria difficult. Genetic studies have identified HLA-B*51 to be the important genetic risk factor. However, the low prevalence of HLA-B*51 in many patients with bone fide disease, especially in non-endemic regions, suggests other factors must also be operative in Behçet syndrome. This consideration is also true for the newly proposed 'MHC-I-opathy' concept. Despite lacking a clear aetiological mechanism and definition, management of manifestations that include major vascular disease (such as Budd-Chiari syndrome and pulmonary artery involvement), eye disease and central nervous system involvement has improved with the help of new technology. Furthermore, even with our incomplete understanding of disease mechanisms, the prognoses of patients with Behçet syndrome, including those with eye disease, continue to improve.

Pulmonary artery aneurysms (PAAs) are well known causes of mortality and morbidity in Behçet disease (BD). However, pulmonary artery involvement in BD is not limited to PAA; the other main type of pulmonary artery involvement is pulmonary artery thrombus (PAT), with or without associated PAA. In addition, other types of lung disease like nodules and cavities in the lung parenchyma are frequently associated with pulmonary artery involvement, and can be misinterpreted as being due to infection. We surveyed the clinical, radiologic, and laboratory characteristics and outcome of 47 BD patients with pulmonary artery involvement and the associated findings, all seen and followed at a single dedicated tertiary care center.We identified 47 (41 male, 6 female) patients in whom pulmonary artery involvement was diagnosed, who were registered in the multidisciplinary clinic at Cerrahpasa Medical Faculty between January 2000 and December 2007. Mean age at diagnosis was 29 ± 8 years, and mean disease duration to the onset of pulmonary artery involvement was 3.6 ± 4.8 years. Hemoptysis was the most common presenting symptom (79%) followed by cough, fever, dyspnea, and pleuritic chest pain. Thirty-four of 47 patients (72%) presented with PAA, including 8 with associated PAT. The remaining 13 patients (28%) had isolated PAT. Patients with isolated PAT in general have clinical features similar to patients with PAA. However, hemoptysis was less frequent and voluminous in patients with isolated PAT. Most (91%) of the patients had active disease outside the lungs when they presented with pulmonary artery involvement.Forty (85%) patients had nodules and 6 (13%) had cavities when first seen. Peripheral venous thrombosis was present in 36 of 47 (77%) patients, and intracardiac thrombi in 12 of the 36 (33%) patients. Nodules, cavities, and intracardiac thrombi were mainly present in the acute stages of pulmonary artery involvement.Pulmonary artery involvement is usually multiple, and involves mostly descending branches of the pulmonary artery. Pulmonary artery involvement may disappear, but arterial stenosis or occlusions usually develop at the same location. After a mean follow-up of 7 years, 12 of 47 (26%) patients were dead; patients with larger aneurysms were more likely to die. Sixteen of 47 (34%) patients were symptom free, and the remaining 40% had mild dyspnea (13/47) and/or small bouts of hemoptysis (8/47).Pulmonary artery pressure may be elevated, and may indicate a poor prognosis. Mediastinal lymphadenopathy and mild pleural and pericardial effusions may also be observed. Corticosteroids and immunosuppressive agents are the mainstays of treatment; however, refractory cases may require embolization, lobectomy, cavitectomy, and decortication.

Takayasu arteritis is a rare inflammatory disease of large arteries. The etiology of Takayasu arteritis remains poorly understood, but genetic contribution to the disease pathogenesis is supported by the genetic association with HLA-B*52. We genotyped ~200,000 genetic variants in two ethnically divergent Takayasu arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. We identified and confirmed two independent susceptibility loci within the HLA region (r(2) < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10(-16)) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10(-9); and rs189754752, OR = 2.47, p = 4.22 × 10(-9)). In addition, we identified and confirmed a genetic association between Takayasu arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10(-12)). The risk allele in this locus results in increased mRNA expression of FCGR2A. We also established the genetic association between IL12B and Takayasu arteritis (rs56167332, OR = 1.54, p = 2.18 × 10(-8)).

No abstract

Objectives Vaccination against COVID-19 emerges as an effective strategy for combating the pandemic. While many of our patients with rheumatic diseases (RD) wonder whether it is safe to get the vaccine, vaccine hesitancy is rising among the general population. We assessed the willingness to get vaccination and its probable predictors among patients with RD compared to healthcare workers and a sample from the general population. Methods We conducted a web-based questionnaire survey in a cross-sectional design in 3 groups of participants just before the mass vaccination program in Istanbul, Turkey. The questionnaire sought socio-demographic variables, COVID-19 related risk factors, willingness to get vaccination, and concerns and thoughts about vaccine. COVID-19 anxiety scale (CAS) was also evaluated. Results We studied in total 732 patients with RD (Group 1), 763 individuals representing general population (Group 2) and 320 hospital workers (Group 3). Dysfunctional anxiety related to COVID-19 was found in 4.9%, 3.8% and 4.1%, in Group 1, 2 and 3, respectively. Of the patients with RD, 29.2% were willing to be vaccinated, 19.0% were unwilling and 51.8% were undecided. These were somewhat similar among the general population (yes: 34.6%, no: 23.3% and unsure: 42.1%), with significantly less undecided individuals (p < 0.001). On the other hand, hospital workers were significantly more willing (yes: 52.5%, no: 20.9% and unsure: 26.6%) ( p < 0.001). Main concerns were probable side effects, unknown scientific results and having no trust. Being male, older age, working in a hospital, not having contracted COVID-19 and high scores on CAS were found to be independently associated with willingness. Conclusions The low rate of vaccine acceptance among patients with RD, as well as general population sampling is worrying. Healthcare policies should aim to implement communication, promote confidence and increase demand for COVID-19 vaccine. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-021-04841-3.

No abstract

We analyzed 1,900 Turkish Behçet’s disease cases and 1,779 controls genotyped with the Immunochip. The most significantly associated single nucleotide polymorphism (SNP) was rs1050502, a tag SNP for HLA-B*51. In the Turkish discovery set, we identified three novel loci, IL1A-IL1B, IRF8, and CEBPB-PTPN1, with genome-wide significance (P<5×10−8) by direct genotyping, and ADO-EGR2 by imputation. ADO-EGR2, IRF8, and CEBPB-PTPN1 replicated by genotyping 969 Iranian cases and 826 controls. Imputed data in 608 Japanese cases and 737 controls replicated ADO-EGR2 and IRF8 and meta-analysis additionally identified RIPK2 and LACC1. The disease-associated allele of rs4402765, the lead marker of the IL1A-IL1B locus, was associated with both decreased interleukin-1α and increased interleukin-1β production. ABO non-secretor genotypes of two ancestry-specific FUT2 SNPs showed strong disease association (P=5.89×10−15). Our findings extend shared susceptibility genes with Crohn’s disease and leprosy, and implicate mucosal factors and the innate immune response to microbial exposure in Behçet’s disease susceptibility.