Skip to main content
Egyptian Rheumatology and Rehabilitation
Download PDF

Evaluation of HLA-B51 frequency and its relationship with clinical findings in patients with Behçet’s disease: 4-year analysis in a single center

Egyptian Rheumatology and Rehabilitation volume 50, Article number: 15 (2023) Cite this article

Abstract

Background

The clinical findings of Behçet’s disease (BD) differ according to the country and race investigated. The most important genetic factor known in the pathogenesis of BD is HLA-B51, and this positivity is high in countries on the “Silk Road” where BD is as frequent as it is in Turkey. Although the positivity of HLA B51 is proven to be high in Turkey, there are no studies in the area of the western Black sea demonstrating its relation to the demographic. We aimed to investigate the association of HLA-B51 positivity in Turkish patients diagnosed as having BD and the relationship between the demographic and clinical findings of the patients.

Results

In this descriptive, cross-sectional study, a convenience sample of adults with BD was obtained from an outpatient clinic of a university hospital in Turkey between January 2018 and January 2022. Patients were diagnosed as having BD according to the criteria of the International BD Study Group, and the patients’ sociodemographic and clinical characteristics were recorded retrospectively. Demographic data and the frequency of clinical findings were compared between patients who were HLA-B51-positive and HLA-B51-negative. Sixty patients (55.6%) were HLA-B51-positive. Oral ulceration, genital ulceration, thrombophlebitis, and family history of BD were found to be higher in patients who were HLA-B51-positive. Erythema nodosum, papulopustular eruption, pathergy positivity, arthritis, and ocular involvement were less frequent in patients with HLA-B51 positivity. However, there were no statistically significant differences according to the frequency of clinical findings between the HLA-B51-positive and HLA-B51-negative groups.

Conclusions

HLA B51 positivity is not diagnostic of BD; however, it may affect clinical phenotypes. Although oral and genital ulcerations, thrombophlebitis, and positive family history of BD were found to be common in patients with HLA-B51 positivity, this relationship could not reach statistical significance.

Background

Behçet’s disease (BD) is a chronic immune-mediated disease, and many different organ systems can be affected. BD has recurrent oral and genital ulcers as a prominent feature and usually follows a relapsing–remitting course [1]. The etiopathogenesis of BD is still unknown, but it is a multifactorial chronic disease triggered by environmental, microbiologic, and immunologic factors in individuals with a genetic predisposition such as human leukocyte antigen (HLA-B51). Although BD generally affects the Middle East, Mediterranean, and East Asian societies on the ancient Silk Road, it can be seen all over the world due to migration. Turkey has the highest prevalence of BD [2,3,4,5,6]. Our study aimed to investigate the association of HLA-B51 positivity in Turkish patients who were diagnosed as having BD and the relationship between the demographic and clinical findings of the patients.

Methods

Study design

This study was cross-sectional and descriptive. The study setting was an outpatient clinic in a tertiary hospital in Turkey.

Ethical statement

The Clinical Research Ethics Committee of the university school of medicine approved the study protocol (Decision no: 2022/109; date: June 6, 2022). All procedures performed in studies with human participants met the ethical standards of the Institutional Research Commission and the 1964 Declaration of Helsinki and its subsequent amendments or comparable ethical standards.

Patient selection

Patients who were diagnosed as having BD according to the criteria of the International Study Group for Behçet Disease (IBSG) had HLA-B51 genetic results [5, 6] and were followed up between January 2018 and January 2022 were included in the study. The electronic records and registration forms of the patients were retrospectively reviewed in the hospital automation system. The exclusion criteria were as follows: (i) age under 18 years and patients with incomplete medical records or follow-ups; (ii) concomitant autoimmune, neurologic, and endocrinologic disease; (iii) patients with malignancy and active infection; (iv) duplicate registration; and (v) patients without HLA-B51 genetic results.

Data collection procedure

The patients’ demographic characteristics (sex, age, family history), clinical features (oral aphthae, genital ulcers, papulopustular lesion, erythema nodosum, thrombophlebitis, pathergy response), and systemic involvement were recorded. Systemic involvement findings were evaluated as mucocutaneous, ocular, musculoskeletal, vascular, neurologic, gastrointestinal system, genitourinary system, cardiac, and pulmonary involvement. Systemic involvements of patients were diagnosed by specialists of the related clinics such as dermatology, ophthalmology, cardiovascular surgery, neurology, gastroenterology, and cardiology as a result of the consultations requested. Findings not related to BD were not recorded. Mucocutaneous findings were clinically evaluated by a dermatologist and patients who had more than three oral ulcers per year during their examinations or in their medical history were regarded as positive for oral ulcers. Patients with active genital ulcers or ulcer scars that were identified by dermatologists were regarded as positive for genital ulcers. Erythema nodosum was diagnosed after clinical evaluation. Pseudo-folliculitis and acneiform lesions detected in patients who were not on steroid treatment were defined clinically as papulopustular lesions by a dermatologist.

Pathergy skin tests indicate hyperactivity of the skin to trauma and are performed using a 20-gauge needle on the antecubital region and evaluated by a dermatologist 48 h later. The presence of papules or pustules is considered positive. In our study, pathergy skin test results were recorded in the files of the patients. Patients with swelling or/and pain around the joints were described as having joint involvement and evaluated using magnetic resonance imaging. Vascular system involvement was diagnosed through clinical observation and Doppler ultrasonography.

Statistical analysis

The sample size was calculated using the G*power program(V3.1.9.2), with a minimum sample size of 64 participants at an α = 0.05 and a power of 80% [7, 8]. The data were analyzed using the IBM SPSS Ver. 23 software package. The compliance of the data to normal distribution was tested using the Kolmogorov–Smirnov test. As descriptive statistics, mean ± standard deviation for numerical variables, min–max, and number and percentage (%) values for categorical variables are given. Student’s t-test was used to compare the two groups. P ≤ 0.05 was considered statistically significant.

Results

The participant recruitment scheme for the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) study is shown in Fig. 1.

Fig. 1
figure 1

The participant recruitment scheme

Full size image

A total of 108 patients who were followed up in the department of physical and rehabilitation outpatient clinic with BD and whose files included HLA-B51 results were included in the study. Of the 108 patients, 74 (68.5%) were female and 34 (31.5%) were male. The patient’s sociodemographic and clinical characteristics are shown in Table 1. The mean age of the patients at the time of diagnosis was 38.53 ± 12.73 years. HLA-B51 was positive in 60 patients and negative in 48 patients. Demographic data and clinical findings were compared between patients who were HLA-B51-positive and HLA-B51-negative. There was no statistically significant difference in the mean age and sex distribution of the patients in the groups (Table 2).

Table 1 Demographic and clinical profiles of the Behçet’s patients
Full size table
Table 2 Gender distribution and mean age of the Behçet patients
Full size table

The clinical features of BD according to HLA-B51 positivity are presented in Table 3. The frequency of oral ulceration, genital ulceration, and thrombophlebitis was found to be higher in patients who were HLA-B51-positive than in those who were HLA-B51-negative, and there were no significant differences between the groups in terms of clinical features. Family history of BD was more frequent in patients who were HLA-B51-positive. The frequency of erythema nodosum, papulopustular eruption, arthritis, and ocular involvement was higher in patients with HLA-B51 negativity; however, the difference between the two groups was not significant. None of the patients had neurologic, gastrointestinal, genitourinary, cardiac, or pulmonary involvement. Pathergy positivity was more common in patients who were HLA-B51-negative than in those who were HLA-B51-positive, but no statistically significant difference was found between the two groups (Table 3).

Table 3 The clinical differences between HLA-B51 positive and negative groups
Full size table

Discussion

BD is an inflammatory disease characterized by recurrent oral aphthous ulcers and various systemic manifestations. BD is more common along the ancient Silk Road, which extends from eastern Asia to the Mediterranean, but is most common in Turkey. The etiopathogenesis is unknown, but it is a multifactorial disease triggered by environmental, microbiologic, and immunologic factors in individuals with a genetic predisposition such as HLA-B51. BD is strongly associated with HLA-B51 in the Turkish population [9]. The present study aimed to investigate the association of HLA-B51 positivity in Turkish patients with BD and the relationship with the demographic and clinical findings. In our study, the frequency of HLA-B51 was 55.6%. Oral and genital ulceration, vascular involvement, and family history were more common in patients with BD with HLA-B51positivity. Erythema nodosum, papulopustular eruption, pathergy positivity, arthritis, and ocular involvement were more common in patients who were HLA-B51-negative. However, there were no significant differences according to the frequency of clinical findings between the two groups.

The age of BD onset is often in the range of 24.7–35.2 years; onset after the age of 50 years and before the age of 20 is very rare [10,11,12]. The disease affects both sexes; however, it is more severe in young men. There are also studies where the number of female patients is higher or equal to the number of male patients [3, 13]. In the present study, the mean age of diagnosis was 38.53 ± 12.73 years, and the male/female ratio was 0.5. The male/female ratio has been reported at different rates according to different geographic regions. In Turkey, the male/female ratio was reported as 1.03 by Türsen et al. [14] and 0.73 by Karıncaoğlu et al. [13]. The ratio can be different according to the geographic region investigated. For example, the male/female ratio was reported as 0.7 in Japan and 1.2 in China [15, 16].

In studies conducted in our country on BD, the prevalence has been reported as 8–42/10,000 [13, 15,16,17,18,19]. Family history has been reported at different rates in patients with BD in Turkey [14, 19, 20]. In our study, family history positivity was 2.7%, and only first-degree relatives were considered positive. Similar to our study, Kalın et al. found family history positivity at 3.9% in their study where only first-degree relatives were considered positive [19].

The etiopathogenesis of BD has not been fully clarified yet, but it is triggered by environmental, microbiologic, and immunologic factors in individuals with a genetic predisposition such as HLA-B51 [21]. There are no pathognomonic laboratory tests to diagnose BD, and as such, the diagnosis is based on clinical criteria. HLA-B51 is known as a genetic marker closely related to BD and is also known to differ between clinical subtypes [22]. In our study, the frequency of HLA-B51 was 55.6%, and there was no difference in terms of HLA-B51 frequency according to age and sex. In the literature, there are conflicting results concerning the association of HLA-B51 with both age and sex. In the Greek population, possession of HLA-B51 alleles carries a high risk for the development of BD, especially at a younger age, and it was reported that men with HLA-B51 were more at risk for BD [23]. In a study conducted on 61 patients with BD from Korea, HLA-B51 status was similar in both sexes, and the patients with HLA-B51 showed significantly earlier onset compared with those without HLA-B51 [24]. In a study reported from Turkey by Akyürek et al., the results showed that there was no correlation between HLA-B51 positivity and age at sex and onset [25].

The prevalence of HLA-B51 may differ according to the populations investigated. Approximately half of all patients with BD are HLA-B51-negative, and also 15% of healthy individuals are found as HLA-B51 positive but do not develop BD in their lifetime [26, 27]. HLA-B51 gene positivity is frequently seen in areas where Turkish tribes immigrated along the Silk Road, and so the frequency of HLA-B51 may differ according to geographic region and ethnicity. The frequency of HLA-B51 was 54–82% [28] in Turkish patients with BD, 44.5% [15] in Japan, and 48.9% [28, 29] in Iran, and it has been reported as 15% [28] in Northern Europe and America. Moreover, it has been reported in the literature that the relationship between HLA-B51’s specific symptoms of BD and the severity of the disease may be different in different ethnic groups [22]. Therefore, the usefulness of HLA-B51 positivity as a diagnostic and prognostic marker in BD remains in doubt [22, 30, 31].

In our study, similar to previous studies, all patients had at least one mucocutaneous finding and the most common was oral ulcers (100%) [32]. Other mucocutaneous findings were papulopustular eruption (19.5%), genital ulcers (13%), and erythema nodosum (10%). Pathergy reaction positivity was present in 7.5%. In a meta-analysis examining the relationship between HLA-B51/B5 clinical features of BD, it was shown that HLA-B51/B5 carriage in BD was associated with increased genital ulcers and ocular and skin symptoms [30]. In the present study, family history, the frequency of oral and genital ulceration, and vascular involvement were found to be more common in patients who were HLA-B51-positive than in those who were HLA-B51-negative. However, there were no statistically significant differences between the groups. The frequency of mucocutaneous findings and ocular and joint involvement was higher in patients with HLA-B51 negativity. Similarly, there were no statistically significant differences between the two groups.

Ocular involvement is an important cause of morbidity in BD. In our study, the frequency of ocular involvement was found as 19.5%, which was lower than reported in the literature [14, 30]. In addition, in the present study, the frequency of ocular involvement was higher in patients who were HLA-B51-negative. The small sample and lack of HLA-B51 subtype analysis may have caused this result. In the literature, it was suggested that patients with the HLA-B51/B5 allele had more ocular or neurologic involvement [30]. However, these observations have not been reported consistently [33], and the discrepancies may have been exacerbated by studies with small sample sizes. In a study conducted in Turkey, Müftüoğlu et al. reported finding no positive or negative association between HLA-B51 and ocular involvement [33]. No association regarding HLAB*51:01 carriage was found with isolated BD manifestations and with ocular involvement in patients with BD from Turkey [28]. Similarly, in an observational study from Turkey, ocular involvement and the type of uveitis showed no correlation with HLA-B51, but it was found that patients who presented with frequent ocular attacks had significantly higher HLA-B51 positivity than patients with rare attacks [34].

In our study, the frequency of vascular involvement was 10.2%, and thrombophlebitis was found more commonly in patients who were HLA-B51-positive. The frequency of vascular involvement was higher in patients who were HLA-B51-positive. However, there were no statistically significant differences between the HLA-B51-positive and HLA-B51-negative groups. Similar to our study, Pamukçu et al. reported vascular involvement at 27% in their study, and they found that the frequency of vascular involvement was higher in patients who were HLA-B51-positive. They also reported that HLA-B51 positivity was not a significant risk factor for vascular involvement [33]. The frequency of arthritis in the present study was 26%. Similar to the literature, the frequency of joint involvement was higher in patients who were HLA-B51-negative, but there were no statistically significant differences according to HLA-B51 status [28, 30, 35].

The present study has some limitations. First, the study was conducted in a single center and had a retrospective design. Second, the impact of HLA-B51 on each clinical manifestation of patients with BD and HLA-B51 subtype analysis could not be examined. Our study is the first to cover the clinical data of a group of patients with BD in the western Black Sea region of Turkey, and we believe that this study will contribute to future larger multicenter studies that will determine whether there are geographic, socioeconomic, and cultural differences across countries, and also investigate the relationship between HLA-B51 and BD in different ethnic groups.

Conclusions

HLA-B51 positivity is not diagnostic of BD; however, it may affect clinical phenotypes. Although oral and genital ulcerations, thrombophlebitis, and positive family history of BD were found to be common in patients with HLA-B51 positivity, this relationship could not reach statistical significance.

Availability of data and materials

The data sets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

BD:

Behçet’s disease

CT:

Computed tomography

HLA B51:

Human leukocyte antigen

IBSG:

International BD Study Group Criteria

References

  1. Kaufman WS, Mcnamara EK (2018) Jorizzo JL Kelley and Firestein’s textbook of rheumatology, 10th edn. Elsevier, Oxford

    Google Scholar 

  2. Verity DH, Marr JE, Ohno S, Wallace GR, Stanford MR (1999) Behcet’s disease, the Silk Road and HLA-B51: historical and geographical perspectives. Tissue Antigens 54(3):213–220. https://doi.org/10.1034/j.1399-0039.1999.540301.x

    Article  CAS  PubMed  Google Scholar 

  3. Alpsoy E (2017) Behcet’s disease: epidemiology. Turkiye Klinikleri J Dermatol-Special Topics 10(4):265–270

    Google Scholar 

  4. Greco A, De Virgilio A, Ralli M, Ciofalo A, Mancini P, Attanasio G, de Vincentiis M, Lambiase A (2018) Behcet’s disease: new insights into pathophysiology, clinical features and treatment options. Autoimmun Rev 17(6):567–575. https://doi.org/10.1016/j.autrev.2017.12.006

    Article  CAS  PubMed  Google Scholar 

  5. Criteria for diagnosis of Behçet’s disease (1990) International Study Group for Behçet’s Disease. Lancet 335:1078-1080. PMID: 1970380

  6. Erdem Sultanoğlu T, Sultanoğlu H (2021) Evaluation of patients with rheumatic diseases admitted at emergency department: 5‐year analysis in a single centre. International Journal of Clinical Practice 75(11):e14837. https://doi.org/10.1111/ijcp.14837

  7. Faul F, Erdfelder E, Lang AG, Buchner A (2007) G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 39(2):175–191. https://doi.org/10.3758/BF03193146

    Article  PubMed  Google Scholar 

  8. Faul F, Erdfelder E, Buchner A, Lang AG (2009) Statistical power analyses using G*Power 3.1: Tests for correlation and regression analyses. Behav Res Methods 41(4):1149–1160. https://doi.org/10.3758/BRM.41.4.1149

  9. Mizuki N, Meguro A, Tohnai I, Gül A, Ohno S, Mizuki N (2007) Association of major histocompatibility complex class I chain-related gene A and HLA-B alleles with Behçet’s disease in Turkey. Jpn J Ophthalmol 51(6):431–436. https://doi.org/10.1007/s10384-007-0473-y

    Article  PubMed  Google Scholar 

  10. Bang DS, Oh SH, Lee KH, Lee ES, Lee SN (2003) Influence of sex on patients with Behçet’s disease in Korea. J Korean Med Sci 18(2):231–235. https://doi.org/10.3346/jkms.2003.18.2.231

    Article  PubMed  PubMed Central  Google Scholar 

  11. Davatchi F, Chams-Davatchi C, Shams H, Shahram F, Nadji A, Akhlaghi M et al (2017) Behcet’s disease:epidemiology, clinical manifestations, and diagnosis. Expert Rev Clin Immunol 13:57–65. https://doi.org/10.1080/1744666X.2016.1205486

    Article  CAS  PubMed  Google Scholar 

  12. Bonitsis NG, Luong Nguyen LB, LaValley MP, Papoutsis N, Altenburg A, Kötter I, Micheli C, Maldini C, Mahr A, Zouboulis CC (2015) Gender-specific differences in Adamantiades-Behçet’s disease manifestations: an analysis of the German registry and meta-analysis of data from the literature. Rheumatology (Oxford) 54(1):121–133. https://doi.org/10.1093/rheumatology/keu247

    Article  CAS  PubMed  Google Scholar 

  13. Karincaoğlu Y, Coşkun BK, Seyhan M, Aki T (2005) Demographical and clinical characteristics of Behçet’s disease patients in Malatya and Elazig. Turkiye Klinikleri J Dermatol 15(2):65–70

    Google Scholar 

  14. Tursen U, Gurler A, Boyvat A. Evaluation of clinical findings according to sex in 2313 Turkish patients with Behçet’s disease (2003) Int J Dermatol 42(5):346–51. https://doi.org/10.1046/j.1365-4362.2003.01741.x.

  15. Mizuki Y, Horita N, Horie Y, Takeuchi M, Ishido T, Mizuki R,et al. The influence of HLA-B51 on clinical manifestations among Japanese patients with Behçet’s disease: a nation wide survey (2020) Mod Rheumatol 30(4):708–14. https://doi.org/10.1080/14397595.2019.1649103.

  16. Zou J, Luo JF, Shen Y, Cai JF, Guan JL (2021) Cluster analysis of phenotypes of patients with Behçet’s syndrome: a large cohort study from a referral center in China. Arthritis Res Ther 23(1):45. https://doi.org/10.1186/s13075-021-02429-7

    Article  PubMed  PubMed Central  Google Scholar 

  17. Idil A, Gürler A, Boyvat A, Çalişkan D, Özdemir O, Işik A, Tunçbilek A, et al (2002) The prevalence of Behcet’s disease above the age of 10 years. The results of a pilot study conducted at the Park Primary Health Care Center in Ankara, Turkey. Ophthalmic Epidemiol 9(5):325–331. https://doi.org/10.1076/opep.9.5.325.10338

  18. Sula B, Batmaz I, Ucmak D, Yolbas I, Akdeniz S (2014) Demographical and clinical characteristics of Behcet’s disease in Southeastern Turkey. Journal of clinical medicine research 6(6):476. https://doi.org/10.14740/jocmr1952w

    Article  PubMed  PubMed Central  Google Scholar 

  19. Kalın ZC, Sarıcaoğlu H, Yazici S, Aydoğan K, Başkan EB. Clinical and demographical characteristics of familial Behçet’s disease (southeast Marmara region) (2019) Dermatology 235(5):407–412. https://doi.org/10.1159/000500820

  20. Borlu M, Ukşal U, Ferahbaş A, Evereklioglu C (2006) Clinical features of Behçet’s disease in children. Int J Dermatol 45:713–716. https://doi.org/10.1111/j.1365-4632.2006.02754.x

    Article  PubMed  Google Scholar 

  21. Takeno M (2022) The association of Behçet’s syndrome with HLA-B51 as understood in 2021. Curr Opin Rheumatol 34(1):4. https://doi.org/10.1097/BOR.0000000000000846

    Article  CAS  PubMed  Google Scholar 

  22. Gül A, Uyar FA, Inanc M, Öcal L, Tugal-Tutkun I, Aral O, Saruhan-Direskeneli G (2001) Lack of association of HLA-B* 51 with a severe disease course in Behçet’s disease. Rheumatology 40(6):668–672. https://doi.org/10.1093/rheumatology/40.6.668

    Article  PubMed  Google Scholar 

  23. Koumantaki Y, Stavropoulos C, Spyropoulou M, Messini H, Papademetropoulos M, Giziaki E, Marcomichelakis N, Palimeris G, Kaklamanis P, Kaklamani E (1998) HLA-B*5101 in Greek patients with Behçet’s disease. Hum Immunol 59(4):250–255. https://doi.org/10.1016/s0198-8859(98)00011-1

    Article  CAS  PubMed  Google Scholar 

  24. Ryu HJ, Seo MR, Choi HJ, Baek HJ (2018) Clinical phenotypes of Korean patients with Behcet disease according to gender, age at onset, and HLA-B51. Korean J Intern Med 33(5):1025–1031. https://doi.org/10.3904/kjim.2016.202

    Article  CAS  PubMed  Google Scholar 

  25. Akyürek FT, Koçak N (2019) Frequency of HLA-B51 in Behçet’s patients and relationship with clinical findings. Turkiye Klinikleri J Dermatol 29(3):108–112. https://doi.org/10.5336/dermato.2019-70625

    Article  Google Scholar 

  26. Kirino Y, Bertsias G, Ishigatsubo Y, Mizuki N, Tugal-Tutkun I, Seyahi E, Kastner DL (2013) Genome-wide association analysis identifies new susceptibility loci for Behcet’s disease and epistasis between HLA-B* 51 and ERAP1. Nat Genet 45(2):202–207. https://doi.org/10.1038/ng.2520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kirino Y, Nakajima H (2019) Clinical and genetic aspects of Behçet’s disease in Japan. Intern Med 58(9):1199–1207. https://doi.org/10.2169/internalmedicine.2035-18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Demirseren DD, Ceylan GG, Akoglu G, Emre S, Erten S, Arman A et al (2014) HLA-B51 subtypes in Turkish patients with Behçet’s disease and their correlation with clinical manifestations. Genet Mol Res 13(3):4788–4796. https://doi.org/10.4238/2014

    Article  CAS  PubMed  Google Scholar 

  29. Davatchi F, Chams-Davatchi C, Shams H, Nadji A, Faezi T, Akhlaghi M, SadeghiAbdollahi B et al (2016) Adult Behcet’s disease in Iran: analysis of 6075 patients. Int J Rheum Dis 19(1):95–103. https://doi.org/10.1111/1756-185X.12691

    Article  CAS  PubMed  Google Scholar 

  30. Maldini C, Lavalley MP, Cheminant M, de Menthon M, Mahr A (2012) Relationships of HLAB51 or B5 genotype with Behcet’s disease clinical characteristics: systematic review and meta-analyses of observational studies. Rheumatology (Oxford) 51(5):887–900. https://doi.org/10.1093/rheumatology/ker428

    Article  PubMed  Google Scholar 

  31. Gül A (2014) Genetics of Behcet’s disease: lessons learned from genomewide association studies. Curr Opin Rheumatol 26(1):56–63. https://doi.org/10.1097/BOR.0000000000000003

    Article  CAS  PubMed  Google Scholar 

  32. Calamia KT, Wilson FC, Icen M, Crowson CS, Gabriel SE, Kremers HM (2009) Epidemiology and clinical characteristics of Behçet’s disease in the US: a population-based study. Arthritis Rheum 61(5):600–604. https://doi.org/10.1002/art.24423

    Article  PubMed  PubMed Central  Google Scholar 

  33. Müftuüǧlu A, Yazıcı H, Yurdakul S, Pazarlı H, Özyazgan Y, Tüzün Y, Yalçın B (1981) BehçET disease: lack of correlation of clinical manifestations with HLA antigens. Tissue Antigens 17(2):226–230. https://doi.org/10.1111/j.1399-0039.1981.tb00687.x

    Article  Google Scholar 

  34. Soylu M, Ersöz TR, Erken E (1992) The association between HLA B5 and ocular involvement in Behçet’s disease in southern Turkey. Acta Ophthalmol 70(6):786–789. https://doi.org/10.1111/j.1755-3768.1992.tb04888.x

    Article  CAS  Google Scholar 

  35. Pamukcu M, Duran TI, Demirag MD (2022) HLA-B51 ımpact on clinical symptoms in Behcet’s disease. J Coll Physicians Surg Pak 32(07):904–908. https://doi.org/10.29271/jcpsp.2022.07.904

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank all the participants of this study.

Funding

We have no funding sources that supported our work.

Author information

Authors and Affiliations

  1. Department of Physical Medicine and Rehabilitation, Düzce University Faculty of Medicine, Düzce, Turkey

    Tuba Erdem Sultanoğlu & Safinaz Ataoğlu

  2. Department of Medical Genetics, Aksaray University Medical Faculty, Aksaray, Turkey

    Recep Eröz

Authors
  1. Tuba Erdem Sultanoğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Recep Eröz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Safinaz Ataoğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

TES, RE, and SA: data collection, writing, and supervision. TES: statistical analyses, supervision, critical analyses, and data collection. The authors read and approved the final manuscript.

Corresponding author

Correspondence to Tuba Erdem Sultanoğlu.

Ethics declarations

Ethics approval and consent to participate

The study protocol was approved by the Clinical Research Ethics Committee (Decision number: 2022/109, date: 06.06.2022). All procedures performed in studies involving human participants were conducted in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Written informed consent was given by all participants.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Erdem Sultanoğlu, T., Eröz, R. & Ataoğlu, S. Evaluation of HLA-B51 frequency and its relationship with clinical findings in patients with Behçet’s disease: 4-year analysis in a single center. Egypt Rheumatol Rehabil 50, 15 (2023). https://doi.org/10.1186/s43166-023-00181-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s43166-023-00181-1

Keywords