Reduced proportions of natural killer T cells are present in the relatives of lupus patients and are associated with autoimmunity

Abstract Introduction Systemic lupus erythematosus is a genetically complex disease. Currently, the precise allelic polymorphisms associated with this condition remain largely unidentified. In part this reflects the fact that multiple genes, each having a relatively minor effect, act in concert to produce disease. Given this complexity, analysis of subclinical phenotypes may aid in the identification of susceptibility alleles. Here, we used flow cytometry to investigate whether some of the immune abnormalities that are seen in the peripheral blood lymphocyte population of lupus patients are seen in their first-degree relatives. Methods Peripheral blood mononuclear cells were isolated from the subjects, stained with fluorochrome-conjugated monoclonal antibodies to identify various cellular subsets, and analyzed by flow cytometry. Results We found reduced proportions of natural killer (NK)T cells among 367 first-degree relatives of lupus patients as compared with 102 control individuals. There were also slightly increased proportions of memory B and T cells, suggesting increased chronic low-grade activation of the immune system in first-degree relatives. However, only the deficiency of NKT cells was associated with a positive anti-nuclear antibody test and clinical autoimmune disease in family members. There was a significant association between mean parental, sibling, and proband values for the proportion of NKT cells, suggesting that this is a heritable trait. Conclusions The findings suggest that analysis of cellular phenotypes may enhance the ability to detect subclinical lupus and that genetically determined altered immunoregulation by NKT cells predisposes first-degree relatives of lupus patients to the development of autoimmunity

VEGF, FGF1, FGF2 and EGF gene polymorphisms and psoriatic arthritis

BACKGROUND: Angiogenesis appears to be a first-order event in psoriatic arthritis (PsA). Among angiogenic factors, the cytokines vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and fibroblast growth factors 1 and 2 (FGF1 and FGF2) play a central role in the initiation of angiogenesis. Most of these cytokines have been shown to be upregulated in or associated with psoriasis, rheumatoid arthritis (RA) or ankylosing spondylitis (AS). As these diseases share common susceptibility associations with PsA, investigation of these angiogenic factors is warranted. METHODS: Two hundred and fifty-eight patients with PsA and 154 ethnically matched controls were genotyped using a Sequenom chip-based MALDI-TOF mass spectrometry platform. Four SNPs in the VEGF gene, three SNPs in the EGF gene and one SNP each in FGF1 and FGF2 genes were evaluated. Statistical analysis was performed using Fisher's exact test, and the Cochrane-Armitage trend test. Associations with haplotypes were estimated by using weighted logistic models, where the individual haplotype estimates were obtained using Phase v2.1. RESULTS: We have observed an increased frequency in the T allele of VEGF +936 (rs3025039) in control subjects when compared to our PsA patients [Fisher's exact p-value = 0.042; OR 0.653 (95% CI: 0.434, 0.982)]. Haplotyping of markers revealed no significant associations. CONCLUSION: The T allele of VEGF in +936 may act as a protective allele in the development of PsA. Further studies regarding the role of pro-angiogenic markers in PsA are warranted

Clinical and cost outcomes from different hyaluronic acid treatments in patients with knee osteoarthritis: evidence from a US health plan claims database

Background: Intra-articular injection of hyaluronic acid (HA) for knee osteoarthritis (OA) effectively reduces pain and delays total knee replacement (TKR) surgery; however, little is known about relative differences in clinical and cost outcomes among different HA products. Objective: To compare disease-specific costs and risk of TKR among patients receiving different HA treatments in a commercially insured cohort of patients with knee OA in the USA. Method: Retrospective analyses using IMS Health’s PharMetrics Plus Health Plan Claims Database were conducted by identifying knee OA patients with claims indicating initiation of HA treatment at an ‘index date’ during the selection period (2007–2010). Patients were required to be continuously enrolled in the database for 12 months preindex to 36 months postindex. A generalized linear model (GLM) with a gamma distribution and log-link function was used to model aggregate patient-based changes in disease-specific costs. A Cox proportional hazards model (PHM) was used to model the risk of TKR. Both multivariate models included covariates such as age, gender, comorbidities, and preindex healthcare costs. Results: 50,389 patients with HA treatment for knee OA were identified. 18,217 (36.2%) patients were treated with HA products indicated for five injections per treatment course (Supartz and Hyalgan). The remainder were treated with HA products indicated for fewer than five injections per treatment course, with 20,518 patients (40.7%) receiving Synvisc; 6,263 (12.4%), Euflexxa; and 5,391 (10.7%), Orthovisc. Synvisc- and Orthovisc-injected patients had greater disease-specific costs compared to Supartz/Hyalgan (9.0%, p<0.0001 and 6.8%, p=0.0050, respectively). Hazard ratios (HRs) showed a significantly higher risk of TKR for patients receiving Synvisc compared to Supartz/Hyalgan (HR=1.069, p=0.0009). Patients treated with Supartz/Hyalgan, Euflexxa, and Orthovisc had longer delays to TKR than those treated with Synvisc. Conclusion: Analysis of administrative claims data provides real-world evidence that meaningful differences exist among some HA products in disease-specific cost and time to knee replacement surgery

Correction: Hyaluronic Acid Injections Are Associated with Delay of Total Knee Replacement Surgery in Patients with Knee Osteoarthritis: Evidence from a Large U.S. Health Claims Database

<p>Correction: Hyaluronic Acid Injections Are Associated with Delay of Total Knee Replacement Surgery in Patients with Knee Osteoarthritis: Evidence from a Large U.S. Health Claims Database</p

Time-to-TKR as a function of number of courses of HA injection.

<p>Each individual comparison of an HA User cohort to HA Non-users was significant (p < 0.0001; see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0145776#pone.0145776.t003" target="_blank">Table 3</a>). All HA cohorts had substantially longer time-to-TKR than HA Non-users (all, p < 0.0001), with the weakest significance for patients who got only 1 course of HA injection (χ² = 13,724.6; p < 0.0001).</p

Correction: Hyaluronic Acid Injections Are Associated with Delay of Total Knee Replacement Surgery in Patients with Knee Osteoarthritis: Evidence from a Large U.S. Health Claims Database

<p>Correction: Hyaluronic Acid Injections Are Associated with Delay of Total Knee Replacement Surgery in Patients with Knee Osteoarthritis: Evidence from a Large U.S. Health Claims Database</p

PRISMA-style diagram.

<p>This Fig summarizes how patients were accrued to the study.</p