HLA antigens in psoriatic arthritis

HLA antigen frequencies were studied in 158 patients with psoriatic arthritis, and compared to those of 101 patients with uncomplicated psoriasis and 243 healthy controls. The HLA antigens B16, B17, B27, B39 and Cw6 were associated with psoriatic arthritis. No associations between DR antigens and psoriatic arthritis were demonstrated. However, the subset of patients with rheumatoid-like arthritis demonstrated an increase in DR4. Uncomplicated psoriasis patients had higher frequencies of B17, Cw6 and DR7 than patients with psoriatic arthritis, while B7 and B27 correlated with development of arthritis. HLA-B27, Cw2 and DRw52 were associated with back involvement, whereas B38 and B39 were associated with polyarthritis. HLA-B7, B13 and DR7 correlated with milder disease in patients with psoriatic arthritis.     

HLA antigens in psoriatic arthritis subtypes of a Spanish population.

HLA-A, B, and C antigens were studied in 104 Spanish patients with psoriatic arthritis. Different clinical features were evaluated and the patients divided into disease subsets. HLA-B17, B27, B16, and Cw6 were the most common haplotypes in the total group. The HLA-B17/Cw6 haplotype was increased in patients with oligoarthritis. The increase of antigen B17 correlated with oligoarthritis and spondarthritis, whereas Cw6 was more significant in oligoarthritis. The prevalence of the B27/Cw1 haplotype was greater in association with spondarthritis and was probably related to the B27.5 subtype linked to Cw1. A significant negative association between the B44/Cw5 haplotype and psoriatic arthritis was found. The existence of several haplotypic factors in the different subsets is discussed. Lack of one or more HLA factors is thought to be responsible for the different clinical forms of psoriatic arthritis.     

Juvenile psoriatic arthritis

Summary Among 664 juvenile chronic arthritis patients cared for in the Out-patient Clinic of the Pediatric Rheumatology Unit of the National Institute of Rheumatology and Physiotherapy 11 were found with juvenile psoriatic arthritis, and their data regarding skin, joint, ophthalmological, laboratory and radiological manifestations were analysed. These patients were categorised according to the four subgroups suggested by Truckenbrodt et al. Considering that the occurrence of the disease is rare, the small number of patients investigated in this study can provide additional data to the study of Truckenbrodt. The higher number of patients with JPA thus studied can give more information for a multicentric evaluation.     

Clinical subgroups and HLA antigens in Italian patients with psoriatic arthritis

The frequencies of HLA antigens were studied in 101 Italian patients with psoriatic arthritis. The total group showed a significant increase in frequency of A1 and B38, and a reduction of B5 when compared to healthy controls. No association between DR and/or DQw antigens and PA were demonstrated. The comparisons between the clinical subgroups and normal controls revealed a significant association of B38 with asymmetric peripheral arthritis, B27 and B39 with spondylitis (with or without peripheral involvement). When intergroup comparison were made, the patients with spondylitis had an increase in frequency of B27 and DQw3 as compared to those with symmetric and asymmetric peripheral disease. DR4 and DRw53 were associated with earlier age of onset of arthritis. There were also significant associations between DQw3 and severe disease, and between A9, B5 and presence of erosions and joint space narrowing. No association with DR4 was showed in a subgroup of patients with symmetric polyarthritis without DIP involvement.     

Disease manifestations and HLA antigens in psoriatic arthritis in northern Sweden

The aim of this study was to identify potential markers of aggressive joint manifestations and HLA associations in patients with psoriatic arthritis (PsA) in northern Sweden. Patients with PsA were examined clinically, with laboratory tests and radiologically. The classification of the disease was based on peripheral and/or axial engagement. HLA B17, B37 and B62 were significantly increased in PsA patients. Univariate analyses suggest that the HLA antigens B37, B62 and some clinical variables were associated with disease course. However, in multivariate analyses distal interphalangeal joint affliction and polyarticular manifestations were the only variables remaining significantly associated with irreversible joint destruction or deformity. There were no significant effects of HLA antigens. In this cross-sectional study, clinical manifestations were more reliable predictors of aggressive joint damage than were specific HLA antigens. However, HLA antigens seemed to modify the expression of the joint disease rather than being involved in joint disease susceptibility. Received: 13 August 2001 / Accepted: 11 February 2002     

Histocompatibility antigens in psoriatic arthritis.

Histocompatibility (HL-A) antigen typing was performed on 82 patients with psoriatic arthritis. The prevalance of HL-AB27 was increased (28%) compared with that in a control group (7-5%), and this was most marked in those with spinal changes. The prevalence in patients with sacroiliitis and syndesmophytes was 75%, with sacroiliitis alone 78%, but with syndesmophytes and normal sacroiliac joints only 36%. The overall prevalence in psoriatic spondylitis was 60%, with a prevalence of 71% in those fulfilling the New York criteria for anklosing spondylitis. The prevalence was not increased in those with only peripheral arthritis (11%). The prevalence of HLA-B13 was decreased in those with psoriatic spondylitis, though this was not statistically significant. The overall prevalence of HLA-BW17 was increased, this being particularly so in those with syndesmophytes, but values were not significant.     

HLA antigens may influence the age of onset of psoriasis and psoriatic arthritis

OBJECTIVE: To analyze whether HLA antigens may influence the age of onset of both psoriasis and psoriatic arthritis (PsA). METHODS: One hundred thirty-five patients with PsA (77 men, 58 women, mean age 47 +/- 12 yrs) were analyzed. All were studied with a standard protocol and consecutively recruited to evaluate the relative contribution of HLA-Cw and HLA-B27 alleles to PsA susceptibility. Fifty patients with psoriasis alone were also recruited to analyze the role of HLA-Cw genes on disease susceptibility. HLA-Cw antigens were investigated by DNA based methods (PCR-SSOP), while HLA-B27 antigen was studied using serological methods, and their frequencies were compared to 177 healthy controls. RESULTS: In PsA Cw6+ patients, the mean age at psoriasis onset was 23 +/- 12 years compared to 32 +/- 12 years in Cw6- patients (p = 0.012). Age of arthritis onset was 35 +/- 13 years in Cw6+ patients versus 38 +/- 12 years in Cw6- patients (p = NS). In patients with psoriasis alone, the age at onset was 18 +/- 10 years in Cw6+ versus 30 +/- 11 years in Cw6- patients (p < 0.01). Cw6 correlated well with a positive family history of psoriasis among first-degree relatives (64% of patients with family history were Cw6+, whereas only 30% of those without family history had this allele (p < 0.05). The onset age of psoriasis in HLA-B27+ patients was 24 +/- 8 years vs 32 +/- 14 years in B27- patients (p = 0.026), whereas onset age of arthritis was 30 +/- 10 years in B27+ compared to an age of onset of 40 +/- 12 in B27- patients (p = 0.0056). CONCLUSION: Our results confirm the known association between Cw6, early onset psoriasis and positive family history (type I psoriasis). The association between HLA-B27 and earlier onset ages for both psoriasis and arthritis in PsA had not previously been emphasized. The HLA antigens may determine not only disease susceptibility, but also the age of disease onset in psoriasis and PsA.     

HLA antigens and seronegative rheumatoid arthritis.

HLA antigens and clinical features in a series of 46 Caucasian patients (40 females, 6 males) and definite repeatedly seronegative rheumatoid arthritis (RA) of more than two years' duration (mean 11.6 years) were compared with those in 77 seropositive RA patients and 110 controls of the same ethnic and geographic origin. Seronegative RA appeared to be less often erosive than seropositive RA, and seronegative patients had fewer extra-articular features. The frequency of the HLA antigen DR1 was raised in seronegative patients as compared with controls (p = 0.006, relative risk = 3) and with seropositive patients (p less than 0.05). HLA-DR4 was slightly increased in seronegative patients compared with controls (p less than 0.05) but was clearly less so than in seropositive patients (p less than 0.005). Early onset of disease was very significantly associated with HLA-DR1 in seronegative patients (p = 0.007), whereas HLA-DR4 was present more frequently in seropositive patients with onset prior to age 35 (p less than 0.05). No correlation between HLA antigens and intolerance to drugs was found in seronegative patients, whereas in seropositive patients side effects to gold salts were associated with DR3. These results suggest that seropositive and seronegative RA have distinct HLA-DR associations, especially in disease of early onset, in addition to well established clinical differences.     

HLA antigens in juvenile arthritis

Serologic HLA typing was performed in 77 patients with juvenile arthritis (JA). The frequency of the DR4 antigen was significantly increased in the seropositive but decreased in the seronegative patients—53% and 17%, respectively (P < 0.025)—compared with 27% in healthy Norwegians. An increased frequency of the HLA-DR4 antigens was also found in polyarticular onset JA (50% compared with 27%, P < 0.05). The frequency of both the HLA-B27 (21%) and the DR5 antigen (21%) was increased in the whole patient group compared with controls (10% and 9%, respectively, P < 0.01). The DR5 antigen was also increased in the systemic onset patients (40%, P < 0.05). Both the DR5 and the DR8 antigens were increased in the pauciarticular onset group (P < 0.05 and P < 0.01, respectively). The results support the view that seropositive and seronegative JA are different disease entities and also that seropositive JA may be an early form of seropositive rheumatoid arthritis. The association between the DR4 antigen and IgM rheumatoid factor suggests that the HLA-DR4 gene or a closely linked gene may regulate autoimmune responses to self IgG.     

HLA DR antigens and disease expression in rheumatoid arthritis.

Ninety-four patients with rheumatoid arthritis who possessed one or more of the HLA DR alloantigens 2, 3, or 4 were studied to investigate the genetic influence on disease severity and prognosis. In those with a disease duration of less than 10 years radiological damage was less in patients with DR2 than in those without this antigen. When current joint scores were compared, patients with this antigen had less evidence of disease than patients with DR3 or 4, DR3 patients having the highest scores. The presence of nodules and Sjögren's syndrome were less common in the DR2 patients. Variability in response to disease modifying drugs according to the patient's HLA DR antigen status may explain these differences. It is concluded, however, that possession of HLA DR2 may be an indicator of good prognosis in patients with rheumatoid arthritis.     

HLA DR antigens in rheumatoid arthritis

The prevalence and possible prognostic significance of HLA-DR antigens have been studied in 129 patients with seropositive (RF-positive) classical rheumatoid arthritis (RA). HLA-DR4 was increased in RA, whilst HLA-DR2 was decreased, though it was not associated with either low titres of RF or with good prognosis. HLA-DR3-positive patients had the highest prevalence of antibodies to nuclear antigens, and the antigen correlated negatively to the presence of subcutaneous nodules, bony erosions and familial RA. RA patients possessing DR3 thus had some of the characteristics of SLE. HLA-DR5 was not present in male RA patients. An absence of familial RA was observed among DRw8-positive patients.     

HLA antigens in juvenile arthritis. Pauciarticular and polyarticular juvenile arthritis are immunogenetically distinct

Using DNA techniques, we investigated the role of HLA-DR, DQ, and DP alleles in susceptibility to juvenile arthritis (JA). We studied 2 groups of patients with JA having a different disease prognosis and course. The pauciarticular form is usually benign, while the polyarticular disease frequently leads to joint destruction and disability. Persistent pauciarticular disease developed preferentially in patients having HLA-DRw13-Dw18 and DQw6-Dw18, but these antigens did not confer susceptibility in patients whose disease converted to the polyarticular form. HLA-DPw2.1 was an additional susceptibility factor for patients with JA of pauciarticular onset. In the polyarticular form of JA, HLA-DPw3 was the major factor for susceptibility, giving a relative risk of 10.3 (P less than 0.0001). In addition, we found that DRw8.1 and DQw4 were increased, and HLA-DR4 was markedly decreased, in patients with pauciarticular and polyarticular disease. These results indicate that in addition to some shared factors, distinct HLA class II alleles are important in pauciarticular or polyarticular JA. We conclude that typing with oligonucleotide probes may be useful in predicting the outcome in some children with arthritis.     

Extraarticular manifestations of rheumatoid arthritis and HLA antigens in northern Italy.

We performed retrospective analysis of 141 Northern Italian patients with rheumatoid arthritis (RA). This series represents all the patients seen as in and/or outpatients at the rheumatologic unit of Reggio Emilia Hospital during a 2 year period (1987-88). We observed a low frequency of nodules (16%) and vasculitis (2.1%). Thus, RA seems to be milder in our population compared to Caucasian patients with RA originating from North America or England. We observed a weak association with DR4 (RR = 2.4) in the total group of patients with RA. A low frequency of DR4 was observed in patients and controls (29 vs 14.5%, p = 0.001). When compared with controls the frequency of DR4 was significantly higher in seropositive (p = 0.001), but not in seronegative patients. We found that DR4 was significantly associated with nodules (RR = 6.4), with extraarticular features (EAF) (RR = 4) and with erosions (RR = 3) compared with controls. The subgroups with nodules and EAF had a DR4 frequency (respectively, of 52 and 40%) which was significantly higher than that observed in remaining patients (respectively, 25 and 24%). No significant difference was observed in the DR4 frequency between the patients with erosions and those without (34 vs 18%). Thus, DR4 in our population seems to be predominantly associated with a subgroup of patients characterized by seropositivity and EAF.