Entheseal involvement in asymptomatic human immunodeficiency virus infected patients: preliminary results of a clinical and ultrasonographic study.

OBJECTIVES: As a strong association between human immunodeficiency virus (HIV) infection and spondyloarthritis (SpA) has been hypothesised, our main objective was to explore by power Doppler ultrasonography (PDUS) the presence of subclinical enthesitis in asymptomatic HIV patients. The presence of subclinical synovitis was also evaluated. METHODS: Consecutive asymptomatic HIV patients were studied and compared with asymptomatic HCV patients and healthy controls (HC). All subjects underwent a clinical and PDUS bilateral examination of the following entheses and joints: epicondyle, quadriceps, patellar, Achilles and plantar fascia; wrists, II and III metacarpo-phalangeal, knee and ankle. RESULTS: Twenty-nine HIV, 32 HCV and 25 HC were recruited; 1.032 entheses and 860 joints were examined. Clinical diagnosis of enthesitis was made in 10.3% HIV patients, 6.2% HCV patients (p=0.66) and none HC (p=0.24). PDUS enthesitis was found in 72.4% HIV, 28.1% HCV (p=0.0008) and 12% HC (p<0.0001). Clinical diagnosis of synovitis was made in 3.4% HIV patients, 9.3% HCV patients (p=0.61) and none HC (p=1). PDUS abnormalities were documented in 24.1% HIV patients, 71.8% HCV patients (p=0.0003) and none HC (p=0.0001). In detecting enthesitis and synovitis, PDUS was more sensitive than clinical examination both in HIV and HCV patients. CONCLUSIONS: Our preliminary study shows the high frequency of PDUS enthesitis in asymptomatic HIV patients, which highlights the close link between HIV and SpA. Further studies are desirable on a larger number of HIV patients to confirm these results. PDUS proved to be more sensitive than clinical examination in detecting subclinical involvement of entheses and joints.

Characterisation of peripheral blood mononuclear cell microRNA in early onset psoriatic arthritis.

OBJECTIVES: To evaluate the micro-RNA (miRNA) expression profile in patients with early psoriatic arthritis (PsA) in order to assess the role of miRNAs as potential PsA biomarkers. METHODS: The expression of 723 mature miRNAs in peripheral blood mononuclear cells of early PsA patients in comparison with early-rheumatoid arthritis (ERA) patients and healthy controls (HC) was evaluated using a miRNA microarray. All patients had active disease and were naïve from treatment. The results were validated for a specific miRNA (miR-21-5p) in the entire series of patients plus an additional group of early PsA, ERA and HC using droplet digital PCR. RESULTS: In PsA, microarray analysis revealed a distinct pattern of 19 (vs. HC) and 48 (vs. ERA) deregulated miRNAs (p<0.05). The significant up-regulation of miR-21-5p both in early PsA and in ERA in comparison with HC was validated and confirmed. In PsA, miR-21-5p was found significantly down regulated after 12 weeks of therapy, which significantly correlated with the reduction of DAPSA score. CONCLUSIONS: In early PsA, a 19- (vs. HC) and 48- (vs. ERA) miRNA signature was identified. A differential expression of miRNAs in patients with active disease makes them attractive biomarkers of psoriatic disease. MiR-21-5p was found up-regulated both in early PsA and ERA, a finding which highlights its role in the inflammatory process in general and its potential role as a therapeutic target in different inflammatory disorders. A potential role of miR-21-5p as a response to treatment biomarker in early PsA has been identified.

The dimeric form of HLA-G molecule is associated with the response of early rheumatoid arthritis (ERA) patients to methotrexate.

A growing body of evidence indicates a possible involvement of HLA (human leukocyte antigen)-G antigens in rheumatoid arthritis (RA), mainly in the HLA-G dimeric isoform, the most active HLA-G form with the strongest immunosuppression, that showed an excellent anti-inflammatory effect in collagen-induced arthritis model mice. However, the relevance of HLA-G dimers in RA response to methotrexate (MTX) treatment is still unknown. We analyzed the HLA-G dimers' amount in plasma samples from early rheumatoid arthritis (ERA) patients before MTX therapy and evaluated the role of these molecules as biomarker of the different response to the treatment. Plasma sHLA-G levels were detected by ELISA, and HLA-G dimeric and monomeric forms were revealed by Western blot in 12 MTX responder (reaching DAS28 remission <2.6) and 8 MTX non-responder (DAS28 ≥5.1) patients before the therapy. The response to MTX was evaluated after 6 months of treatment. All ERA patients reaching remission showed higher plasma sHLA-G levels and the 78 kDa HLA-G dimeric form. Unresponsive ERA patients were characterized by lower plasma sHLA-G levels, and only one patient presented the 78 kDa HLA-G dimeric form (DAS28 5.1). Our preliminary results support the hypothesis that in ERA patients, sHLA-G and, in particular, the presence of the dimeric form in plasma samples before MTX therapy could be an a priori biomarker for the response to MTX treatment.

HLA-G may predict the disease course in patients with early rheumatoid arthritis.

The current management of early rheumatoid arthritis (ERA) is to start an intensive treatment as soon as possible. To avoid under/overtreatment, it is important to identify reliable ERA evolution biomarkers. HLA-G molecules has been associated with rheumatoid arthritis, suggesting a role in disease regulation. HLA-G antigens are expressed as membrane bound and soluble isoforms (mHLA-G, sHLA-G) that act as ligand for immune-inhibitory receptors (ILT2, ILT4, KIR2DL4). Expression of HLA-G is influenced by a 14 bp insertion/deletion polymorphism in exon 8 of the gene, where the deletion is associated with mRNA stability. We analyzed 23 ERA patients during a 12 months follow-up disease treatment for sHLA-G, IL-1beta, IL-6, IL-10 and TNF-alpha levels in plasma samples by ELISA, mHLA-G and ILT2 expression on peripheral blood CD14 positive cells by flow cytometry and typed HLA-G 14 bp deletion/insertion polymorphism by Real-Time PCR. Disease status (DAS28), ultrasonography with power Doppler and laboratory data were checked. Cytokine levels confirmed the anti-inflammatory effect of the treatment. sHLA-G, mHLA-G and ILT2 expression inversely correlated with DAS28 disease scores. The frequency of 14 bp deletion allele increased in patients with disease remission. Based on these results, HLA-G may be a candidate biomarker to evaluate early prognosis and disease activity in ERA patients.