1. Background
Seronegative Spondyloathropathies (SNSAs) are defined as a group of diseases with the same clinical demonstrations and genetic characteristics [1]. There is six subtype of SNSAs contains Ankylosing Spondylitis (AS), psoriatic arthritis, entropathic arthropathy, reactive arthritis, Juvenile Rheumatoid Arthritis (JRA) and undifferentiated spondyloarthropathies [1].
Human leukocyte antigen system or HLA refers to four gene families (know with A - D letters) that codify a series of polymorphic proteins on most nucleated cell surfaces in human body [2]. The role of HLA system in many rheumatologic disorders has been known [3]. HLA-B27 is a type of these genetic factors that have different prevalence in various rheumatologic diseases [3]. In SNSAs presence of HLA-B27 is very prevalent but the exact prevalence is unknown [4, 5]. Different values have been reported in previous studies for example in one study 43% of SNSAs patients were HLA-B27 positive while in another study it was 90% [4, 6]. HLA-B27 prevalence varies among different races. In a 2009 US national survey 7.5% of non-Hispanic whites, 4.6% of non-Hispanic blacks and 1.1% of Mexican-Americans were HLA-B27 positive [7]. In general, an individual’s risk of developing AS is increased 5.6-fold to 16-fold if there is a first degree relative with AS. This risk depends partly upon the presence of HLA-B27; 10 - 20% of HLA-B27 positive individuals with affected first degree relatives develop AS [8]. According to importance of HLA-B27 prevalence determination, controversies in different articles and cross racial varieties this study was conducted on Kashan’s SNSA patients.
2. Objectives
Due to lack of data about HLA-B27 prevalence in patient with SNSA in Kashan this study was conducted to determine the status of HLA-B27 in these patients.
3. Patients and Methods
In this cross sectional study 294 patients suffered from SNSAs were evaluated. Patients were selected from hospitalized known cases or outpatient referrers of Kashan’s rheumatology clinic, randomly. All patients were diagnosed during 2005 to 2010 years and were under standard treatment of SNSAs.
After providing details on how to conduct the study, patient’s consent was obtained to participate in the study. Demographic information such as age, gender, disease duration and family history was obtained and were recorded in a questionnaire. Type of disease was extracted from medical records and recorded in questionnaire.
All patients were examined by a rheumatologist and disease manifestations (such as peripheral and axial joints engagement) were recorded. Five milliliters venous blood was obtained from patient’s cubital fossa and HLA-B12 were determined by flow cytometery method using BD™ HLA-B27 Kit produced by United Kindom. Data were analyzed by windows SPSS-16 using t-test and χ2 tests. Results reported as Mean ± Standard Deviation. Statistical significance was set at P < 0.05.
4. Results
Of all patients 26.8% (167 subjects) were male and 43.2% (127 subjects) were female. Average age of the patients was 29.5 ± 13.5 years. Average disease duration was 3.5 ± 3.2 years. Antrropathic arthropathy was observed in 22.4% (66 subjects) of the patients. Then, reactive arthritis, psoriatic arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis and finally undifferentiated spondiloarthropathies were observed in 19.1% (56 subjects), 18.4% (54 subjects), 16.3% (48 subjects), 14.3% (42 subjects) and 9.5% (28 subjects) patients, respectively. First degree relative background was positive in 12.6% (37 subjects) patients.
In 84.4% (248 subjects), peripheral joint engagement was observed. Of all patients 34.7% (120 patients) had axial joint engagement. Extra articular engagement was also observed in 59.2% (147 patients). HLA-B27 was reported positive in 26.5% of patient with seronegative spondyloarthropathies. The study findings are reported in Table 1.
| Variable | Positive | Negative | Sum Patients | P Value |
|---|---|---|---|---|
| < 0.001 | ||||
| Male | 57 (34.1) | 110 (65.9) | 167 | |
| Famale | 21 (16.5) | 106 (83.5) | 127 | |
| Total | 78 (26.5) | 216 (73.5) | 294 | |
| < 0.001 | ||||
| Juvenile rheumatoid arthritis | 6 (12.5) | 42 (87.5) | 48 | |
| Reactive arthritis | 9 (16.1) | 47 (83.9) | 56 | |
| Undifferentiated SpA | 5 (17.9) | 23 (82.1) | 28 | |
| Entropathic arthropathy | 12 (18.2) | 54 (81.8) | 66 | |
| Psoriatic arthritis | 17 (31.5) | 37 (68.5) | 54 | |
| Ankylosing spondylitis | 29 (69) | 216 (73.5) | 45 | |
| Total | 78 (25.6) | 216 (73.5) | 294 | |
| < 0.001 | ||||
| Yes | 26 (70.3) | 11 (29.7) | 37 | |
| No | 52 (20.2) | 205 (79.8) | 257 | |
| Total | 78 (26.5) | 216 (73.5) | 294 | |
| < 0.001 | ||||
| Yes | 55 (22.2) | 193 (77.8) | 248 | |
| No | 23 (50) | 23 (50) | 46 | |
| Total | 78 (26.5) | 216 (73.5) | 294 | |
| < 0.001 | ||||
| Yes | 53 (52) | 49 (48) | 102 | |
| No | 25 (13) | 167 (87) | 192 | |
| Total | 78 (26.5) | 216 (73.5) | 294 | |
| 0.4 | ||||
| Yes | 49 (28.2) | 125 (71.8) | 174 | |
| No | 29 (24.2) | 91 (75.8) | 120 | |
| Total | 78 (26.5) | 216 (73.5) | 294 |
Abundance Distribution of HLA-B27 in Patients With Seronegative Spondyloarthropathies, According to the Patients Profiles in Kashan From 2005 to 2010
The study results show that HLA-B27 was positive in one-fourth of the patients with one of seronegative spondyloarthropathies. HLA-B27 was more prevalent in males than females. Among seronegative spondyloarthropathies, HLA-B27 was the most prevalent and ankylosing spondilits (69%) was the least prevalent one in juvenile rheumatoid arthritis (5-12%). Prevalence of HLA-B27 amongst patients with positive family background was more than those with no background.
5. Discussion
In this study we found that prevalence of HLA-B27 in Kashan’s SNSAs patients were 26.5%. Prevalence of this kind of HLA was twice in males than females which was statistically significant. Wu et al. [9] reported prevalence of HLA-B27 in patients with SNSAs about 40%, Buschiazzo et al. reported 45% without sexual separation [10]. Mijiyawa et al. reported positive HLA-B27 in of African patients with SNSAs [11]. They reminded that HLA-B27 is not a suitable marker to diagnose these diseases in Africans while others consider the relation between HLA-B27 and serongative spondyloarthropathies as an obvious example of relation between a group of diseases and a special heritage marker [11].
Adib et al. reported prevalence of HLA-B27 in general population of Iran about 3% in their study [12]. They noted that prevalence level of HLA-B27 is limited to Caucasians and is similar to its abundance in Arabs, Jews and Armenians. A relatively low prevalence of HLA-B27 in the general population and its 25 - 65% prevalence among seronegative spondyloarthropathies patients can show the relation between this marker and each type of diseases [12].
In the present study prevalence of HLA-B27 among patients with seronegative spondyloarthropathies was mostly observed in ankylosing splodytis so that about 70% of them had positive HLA-B7, while after, prevalence was observed in patients with psoriatic arthritis, entropathic arthropathy and undifferentiated spondiloarthropathy. In two studies of De Keyser et al. and Reveille, prevalence of HLA-B27 in ankylosing spondylitis patients was along with the present study results and reported about 90 to 95% which was more than the present results [13, 14].
De Keyser et al. studied patients with reactive arthritis after ankylosing spondylitis in which HLA-B27 was positive for about 80% of them [13]. Reveille has also reported prevalence of HLA-B7 for reactive arthritis as the second rank and about 70 - 90% which is five times more than that of the antigen in the present study [14]. De Keyser et al. have discussed HLA-B27 prevalence in psoriatic arthritis patients after reactive arthritis and ankylosing spondylitis. They have reported it about 40% which is a little more than the present study. About 13% of the studied patients had a positive family background of seronegative spondiloarthropathy [13]. HLA-B27 was 70% prevalent in these patients while HLA-B27 prevalence was about 20% in patients with no family background of seronegative spondiloarthropathy diseases [13]. This difference which shows more prevalence of HLA-B27 in positive family background was statistically significant.
In Buschiazzo et al. study a positive family background was observed in 16.8% of the patients with seronegative spondiloarthropathy, so this study results are similar and a little more than present study [10]. According to the results it seems that HLA-B27 prevalence in patients with spondiloarthropathy in Kashan was low and it may not be used as a strong significant experimental criterion. As there is a high relationship between HLA-B27 in patients with family background, relation between positive family background and HLA-B27 can be used as a trustful reliable criterion to diagnose diseases and patients. Complementary studies are recommended as comparisons between patient and control groups to reach clearer results.
