Familial aggregation of psoriatic arthritis Chandran, V; Schentag, C T; Brockbank, J E ...
Annals of the rheumatic diseases,
05/2009, Letnik:
68, Številka:
5
Journal Article
Recenzirano
The aim of this study was to determine the recurrence risk of psoriatic arthritis (PsA) and uncomplicated psoriasis in first-degree relatives (FDRs) of patients with PsA.
All available FDRs (full ...siblings, parents and children) of 100 consecutive consenting patients attending a PsA clinic were evaluated for the presence of psoriasis and PsA using a standard protocol. The protocol included a screening questionnaire, physical examination by a rheumatologist, and radiographic and laboratory assessment. The prevalence of PsA and psoriasis in FDRs of the index cases was determined, and the recurrence risk ratio (lambda) was calculated, assuming a population prevalence of PsA of 0.25%, and a population prevalence of psoriasis of 2%.
The 100 probands had 533 relatives. Eighty-four of them were deceased and 53 were unavailable (age <16 years). Of the remaining 396 FDRs, 107 did not participate (living too far away/did not consent). Thus, 289/396 (73%) of the available FDRs participated in the study. There were 130 siblings, 108 parents and 51 children. The prevalence of PsA and psoriasis among FDRs was 7.6% and 15.2%, respectively. The lambda(1 )was 30.4 for PsA and 7.6 for psoriasis. The prevalence of PsA and psoriasis in siblings was 7.7% and 17.7%, respectively. The lambda(S) was 30.8 for PsA and 8.8 for psoriasis.
The recurrence risk ratio for both PsA and psoriasis is high in FDRs and siblings of patients with PsA. These results confirm that both PsA and psoriasis have a strong heritable component.
Objective. Biomarkers may be helpful in screening patients with psoriasis for PsA. Our purpose was to identify serum biomarkers for psoriasis and PsA. Methods. Fifty-two patients with psoriasis (26 ...satisfying CASPAR classification criteria for PsA) and 26 healthy controls were recruited for our study. Patients with psoriasis and PsA were group matched for age, sex and psoriasis duration, whereas controls were matched for age and sex. Blood samples were drawn at the time of assessment and serum was analysed for the following: IL-12, IL-12p40, IL-17, TNF super family member 14 (TNFSF14), MMP-3, RANK ligand (RANKL), osteoprotegerin (OPG), cartilage oligomeric matrix protein (COMP), C-propeptide of Type II collagen (CPII), collagen fragment neoepitopes Col2-3/4long mono (C2C) and Col2-3/4short (C1-2C) and highly sensitive CRP (hsCRP). Data were analysed using logistic regression and receiver operating characteristic curves were plotted. Results. Fifty-two patients with psoriatic disease had a mean age of 46 years and psoriasis duration of 16.8 years. Compared with controls, increased serum levels of RANKL, TNFSF14, MMP-3 and COMP independently associated with psoriatic disease (P < 0.05). Twenty-six PsA patients (mean swollen and/or tender joint count 16, swollen joint count 5) were then compared with 26 patients who had psoriasis alone. Increased levels of hsCRP, OPG, MMP-3 and the CPII : C2C ratio were independently associated with PsA (P < 0.03). Conclusion. This pilot study indicates that hsCRP, OPG, MMP-3 and the CPII : C2C ratio are biomarkers for PsA in patients with psoriasis.
BACKGROUND: As part of assessing the possibility of transfusion transmission of human herpesvirus 8 (HHV‐8 or Kaposi's sarcoma‐associated herpesvirus), HHV‐8 seroprevalence was estimated among US ...blood donors, the performance of HHV‐8 serologic tests was compared, and the presence of HHV‐8 DNA was tested for in donated blood.
STUDY DESIGN AND METHODS: Replicate panels of 1040 plasma specimens prepared from 1000 US blood donors (collected in 1994 and 1995) and 21 Kaposi's sarcoma patients were tested for antibodies to HHV‐8 in six laboratories. HHV‐8 PCR was performed on blood samples from 138 donors, including all 33 who tested seropositive in at least two laboratories and 22 who tested positive in at least one.
RESULTS: The estimated HHV‐8 seroprevalence among US blood donors was 3.5 percent (95% CI, 1.2%‐9.8%) by a conditional dependence latent‐class model, 3.0 percent (95% CI, 2.0%‐4.6%) by a conditional independence latent‐class model, and 3.3 percent (95% CI, 2.3%‐4.6%) by use of a consensus‐derived gold standard (specimens positive in two or more laboratories); the conditional dependence model best fit the data. In this model, laboratory specificities ranged from 96.6 to 100 percent. Sensitivities ranged widely, but with overlapping 95 percent CIs. HHV‐8 DNA was detected in blood from none of 138 donors evaluated.
CONCLUSIONS: Medical and behavioral screening does not eliminate HHV‐8‐seropositive persons from the US blood donor pool, but no viral DNA was found in donor blood. Further studies of much larger numbers of seropositive individuals will be required to more completely assess the rate of viremia and possibility of HHV‐8 transfusion transmission. Current data do not indicate a need to screen US blood donors for HHV‐8.
We conducted a case-control study to determine the association between KIR2D and KIR3D gene polymorphisms and their interaction with HLA alleles in PsA.
A total of 678 subjects with PsA and 688 ...healthy controls were studied. Differences between cases and controls in the frequency of individual KIR polymorphisms were tested for significance by an asymptotic χ(2) test and Fisher's exact test. Trends for increasing susceptibility to PsA from combined genotypes (HLA-KIR and HLA) were evaluated by the Cochran-Armitage trend test. Multigene logistic regression analysis was conducted to identify independent associations and interactions.
In univariate analyses, KIR2DL2 and KIR2DS2 polymorphisms were significantly associated with PsA. Only KIR2DS2 was associated with PsA compared with healthy controls in multivariate analysis odds ratio (OR) 1.25, 95% CI 1.01, 1.54, P = 0.044. The presence of HLA-C group 2 alleles was associated with a higher risk of PsA (trend test P = 0.006). The risk of PsA is higher when KIR2DS2 is present with the HLA-C ligands (C group 1) for the corresponding inhibitory KIRs, and is highest when KIR2DS2 is present in the absence of HLA-C ligands for homologous inhibitor KIRs, compared with the state when KIR2DS2 is absent (trend test P = 0.027). The presence of HLA-C alleles that have high cell surface expression was also associated with a higher risk of PsA (trend test P < 0.001). HLA-B Bw4 and HLA-B Bw4 80ile allele groups were associated with a higher PsA risk (trend test P < 0.0001 for both analyses).
This study confirms the association of the KIR2DS gene, especially KIR2DS2, with PsA.
Psoriasis vulgaris (PsV) risk is strongly associated with variation within the major histocompatibility complex (MHC) region, but its genetic architecture has yet to be fully elucidated. Here, we ...conducted a large-scale fine-mapping study of PsV risk in the MHC region in 9,247 PsV-affected individuals and 13,589 controls of European descent by imputing class I and II human leukocyte antigen (HLA) genes from SNP genotype data. In addition, we imputed sequence variants for MICA, an MHC HLA-like gene that has been associated with PsV, to evaluate association at that locus as well. We observed that HLA-C∗06:02 demonstrated the lowest p value for overall PsV risk (p = 1.7 × 10−364). Stepwise analysis revealed multiple HLA-C∗06:02-independent risk variants in both class I and class II HLA genes for PsV susceptibility (HLA-C∗12:03, HLA-B amino acid positions 67 and 9, HLA-A amino acid position 95, and HLA-DQα1 amino acid position 53; p < 5.0 × 10−8), but no apparent risk conferred by MICA. We further evaluated risk of two major clinical subtypes of PsV, psoriatic arthritis (PsA; n = 3,038) and cutaneous psoriasis (PsC; n = 3,098). We found that risk heterogeneity between PsA and PsC might be driven by HLA-B amino acid position 45 (pomnibus = 2.2 × 10−11), indicating that different genetic factors underlie the overall risk of PsV and the risk of specific PsV subphenotypes. Our study illustrates the value of high-resolution HLA and MICA imputation for fine mapping causal variants in the MHC.
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