Development Of Polyarthritis Research Articles

Portrait of a patient with systemic lupus erythematosus for the prescription of the type I interferon inhibitor anifrolumab

In recent years the use of monoclonal antibodies that block activity of type I interferon (IFN) or its receptors has become the new approach in the pharmacotherapy of systemic lupus erythematosus (SLE).Objective: to characterize patients with SLE treated with the type I IFN receptor inhibitor anifrolumab (AFM, Saphnelo®).Material and methods. The prospective 12-month study included 21 patients with SLE who met the 2012 SLICC criteria. Standard laboratory and immunological markers for SLE were examined in all patients. The SLEDAI-2K index was used to determine the activity of SLE and the CLASI index was used to determine the severity of the mucocutaneous syndrome. Organ damage was assessed using the SLICC/ACR Damage Index (DI). The LupusQol and FACIT-Fatigue questionnaires were used to analyze health-related quality of life (HRQoL).Results and discussion. Female patients prevailed in the study, female/male ratio – 17 (81%)/4 (19%), median age – 31 [27; 46] years, disease duration – 9 [6.0; 11.0] years. The majority of patients (86%) had moderate or high disease activity according to the SLEDAI-2K index. Among the clinical manifestations of SLE, skin and mucous membranes lesions predominated (81%). Non-erosive polyarthritis of varying severity was observed in 66% of cases. Serositis showed 24% of patients (pleurisy, pericarditis), 43% had hematological abnormalities (hemolytic anemia, leukopenia, lymphopenia) and 14% - urinary syndrome (daily proteinuria up to 0.5 g/l and/or urinary sediment – leukocytes/erythrocytes/cylinders up to 5 in the field of view in the absence of urinary tract infection). All patients had immunological disorders. 14% of them were diagnosed with antiphospholipid syndrome (APS) and 43% with Sjögren's syndrome.All patients received hydroxychloroquine, 95% received glucocorticoids (GC) from 5 to 60 mg/day, 66% received immunosuppressants (cyclophosphamide, mycophenolate mofetil, azathioprine, methotrexate). 33% of patients had anamnesis of treatment with biologic disease modifying antirheumatic drugs (rituximab, belimumab, dual anti-B-cell therapy) and Janus kinase inhibitor baricitinib. All patients experienced a significant deterioration in HRQoL.Conclusion. The indications for prescribing AFM to 21 patients with SLE were: active SLE according to SLEDAI-2K and/or CLASI with predominant involvement of skin, its appendages and development of polyarthritis with immunological disorders, intolerance/ineffectiveness of previous standard therapy and inability to achieve low average daily doses of oral GCs. Other clinical manifestations in some patients were: serositis, mild hematological disorders (Coombs-positive anemia, leukopenia), urinary syndrome. AFM could be prescribed for a combination of SLE with secondary APS and Sjögren's syndrome as well as for a high DI SLICC.

Methylsulfonylmethane alone or in combination with thiocolchicoside modulate autoimmune disease in rats with adjuvant arthritis

Many active anti-arthritic natural substances are revealed into the past years. The aim of study was to assess the combined efficacy of methylsulfonylmethane (MSM) with thiocolchicoside (Th) (compound MTh) and MSM alone against adjuvant-induced arthritis (AA) in rats. In the first experiment 30 rats and in the second - 21 ratswere randomly divided into 6 groups: I gr. - AA + MSM (77 mg/kg), II and V gr. - AA + diclofenac (DF), III and VI gr. - the control AA groups without treatment, IV gr. - MTh (38 mg/kg). DF (1 mg/kg) in both experiments was used as a reference drug. 6 rats were as the healthy control group. AA rats were treated from day 0 to 17. All preparations were suspended in 0.5 ml of 1℅ starch gel and injected orally 5 days a week. Body weight and joint swelling were monitored 3 times a week. Development of polyarthritis, blood indices, pro-/antioxidant activity and pro-inflammatory cytokines in blood serum, and histopathology of the liver and paw were assessed at the end of experiment. MSM significantly decreased joint swelling on days 3 and 13. MTh in twice lower dose more markedly suppressed joint swelling and also significantly reduced the changes in soft periarticular tissues, synovium and cartilage as compared to the control AA group. Both preparations alleviated infiltration with inflammatory cells and synovial proliferation, as well as protected cartilage destruction and decreased pannus formation. MSM and MTh improved the blood indices and insignificantly suppressed IL-17. They markedly decreased the level of malondialdehyde (MDA). Some anti-oxidant activity of preparations was also confirmed. No toxic effects on the liver were revealed. MSM and MTh attenuated the development of AA in rats. Combination therapy was more effective than single MSM and required the twice lower doses to receive the beneficial anti-arthritic effect. Both preparations could be the potential preventive or therapeutic candidates for the treatment of autoimmune processes in combination with other drugs.

Antiinflammatory effect of herbal preparations on adjuvant arthritis in rats

The present study aimed to investigate the antiinflammatory effects of 2 herbal extracts (CDS and CDSM) in rats with experimental adjuvant arthritis (AA). Joint swelling, development of polyarthritis, blood indices, pro/antioxidant activity, and proinflammatory cytokine IL-17 in blood serum, as well as the liver and paw histopathology and histochemistry, were assessed. Oral injections of extracts showed an antiinflammatory effect analogous to that of diclofenac (DF), improved blood indices and suppressed level of IL-17, significantly diminished joint swelling, and histological changes in the joints. Increase in CAT activity and AOA and reduction in lipid peroxidation was noted. The preparations did not show toxic effects on the liver. The obtained results suggest that the prophylactic use of CDS and CDSM have a significant effect on slowing AA progression, similar to the effect of DF. Both preparations could be potential preventive or therapeutic candidates for the treatment of autoimmune processes in combination with other drugs.

Autoimmune Arthritides, Rheumatoid Arthritis, Psoriatic Arthritis, or Peripheral Spondyloarthritis Following Lyme Disease.

To describe systemic autoimmune joint diseases that develop following Lyme disease, and to compare their clinical features with those of Lyme arthritis (LA). We reviewed records of all adult patients referred to our LA clinic over a 13-year period, in whom we had diagnosed a systemic autoimmune joint disease following Lyme disease. For comparison, records of patients enrolled in our LA cohort over the most recent 2-year period were analyzed. Levels of IgG antibodies to Borrelia burgdorferi and to 3 Lyme disease-associated autoantigens were measured. We identified 30 patients who had developed a new-onset systemic autoimmune joint disorder a median of 4 months after Lyme disease (usually manifested by erythema migrans [EM]). Fifteen had rheumatoid arthritis (RA), 13 had psoriatic arthritis (PsA), and 2 had peripheral spondyloarthritis (SpA). The 30 patients typically had polyarthritis, and those with PsA or SpA often had previous psoriasis, axial involvement, or enthesitis. In the comparison group of 43 patients with LA, the usual clinical picture was monoarticular knee arthritis, without prior EM. Most of the patients with systemic autoimmune joint disorders were positive for B burgdorferi IgG antibodies, as detected by enzyme-linked immunosorbent assay, but had significantly lower titers and lower frequencies of Lyme disease-associated autoantibodies than patients with LA. Prior to our evaluation, these patients had often received additional antibiotics for presumed LA, without benefit. We prescribed antiinflammatory agents, most commonly disease-modifying antirheumatic drugs, resulting in improvement. Systemic autoimmune joint diseases (i.e., RA, PsA, SpA) may follow Lyme disease. Development of polyarthritis after antibiotic-treated EM, previous psoriasis, or low-titer B burgdorferi antibodies may provide insight into the correct diagnosis.

Effect of Gold Nanoparticles in the Treatment of Established Collagen Arthritis in Rats

The role of gold nanoparticles (AuNPs) in the treatment of autoimmune diseases remains vague. Therefore, the aim of this study was to determine the effect of AuNPs in the treatment of rats with established collagen-induced arthritis (CIA). A total of 24 Wistar male rats with established CIA were used. AuNPs measuring 13-nm and 50-nm were prepared according to standard procedures, and their size was determined using transmission electron microscopy. These gold particles were injected intra-articularly 5 times a week, 12 injections in total. Body and organ weight, arthritic profiles based on paw swelling, histological changes in the joints and internal organs, blood indices, and serum oxidative products were investigated. An examination of the course of the experimental disease and a subsequent histological analysis as well as hematological studies revealed a nontoxic effect of AuNPs on the vital organs. The treatment of the rats with established CIA by 13-nm and 50-nm gold nanoparticles decreased joint swelling by 49.7% (P<0.002) and 45.03% (P<0.01), respectively. That corresponded to the decrease in statistically significant histological changes in articular tissues. AuNPs showed their antioxidant effect by increasing the level of antioxidant enzyme catalase. The continuous intra-articular administration of AuNPs not only reduced the inflammation, joint swelling, and development of polyarthritis, but also reduced histological changes in articular tissues without toxic effects on the internal organs. The results obtained disclose the role of AuNPs as antioxidant agents.

Anti-inflammatory activity of some potassium salts of N,N-disubstituted 4-aminoazobenzenesulfonic acids in rat adjuvant arthritis

Anti-inflammatory effects of three potassium salts of N,N-disubstituted 4-aminoazobenzenesulfonic acids were investigated and compared to that of acetylsalicylic acid (ASA) in rats with adjuvant arthritis (AA). Prophylactic oral administration of all compounds in a dose of 150 mg/kg ameliorated AA symptoms in animals. The most pronounced anti-inflammatory activity at the end of the experiment showed compound 1 containing imino group: it significantly suppressed joint swelling by 48.2% in female and by 44.2% in male rats with AA. The development of polyarthritis after the treatment with this compound was the lowest in female (20%) and male (40%) rats (in control--100% of animals with polyarthritis). All derivatives, and especially compound 1, also improved the systemic parameters of disease such as blood indices and internal organs' weight, and showed no toxicity on the main organs such as liver and spleen.

HLA-DRB1 genotyping in patients with juvenile idiopathic arthritis in Taiwan.

The object of this study was to investigate whether there is an association between HLA-DRB1 alleles and the development of juvenile idiopathic arthritis (JIA) in Taiwan. HLA-DRB1 alleles were studied in 60 patients with JIA and 200 healthy controls using polymerase chain reaction (PCR)/sequence-specific oligonucleotide probes (SSO). The frequency of HLA-DRB1*0405 in patients with JIA was found to be significantly higher than that in healthy controls [odds ratio (OR) 2.64, 95% confidence interval (CI) 1.01-6.91]. The DRB1*0405 allele was significantly associated with the development of both polyarthritis (OR 4.30, 95% CI 1.34-13.80) and oligoarthritis (OR 3.27, 95% CI 1.01-10.58). The frequency of HLA-DRB1*1502 was higher in Taiwanese JIA patients with systemic arthritis than in controls (OR 18.09, 95% CI 2.25-145.73). We conclude that, in Taiwan, HLA-DRB1*0405 is associated with the development of polyarthritis and oligoarthritis in children, and HLA-DRB1*1502 is associated with the development of systemic arthritis.

Chronic treatments with aspirin or acetaminophen reduce both the development of polyarthritis and Fos-like immunoreactivity in rat lumbar spinal cord

We have previously shown that during the development of adjuvant-induced arthritis (AIA), and without any peripheral stimulation, the number of Fos-like immunoreactive (Fos-LI) neurons in lumbar spinal cord increases in parallel with the clinical and behavioral signs of the disease and peaks 3 weeks after the inoculation which corresponds to the maximal stage of hyperalgesia (Abbadie and Besson 1992a). The aim of this study was to evaluate the suitability of the Fos-LI technique to gauge the effects of the two most prescribed analgesics, aspirin and acetaminophen (paracetamol), on spinal cord neurons of polyarthritic rats. The effects of the two drugs were tested on the “evoked” Fos-LI induced by peripheral mechanical noxious stimulus, as well as the effects of a chronic treatment on “basal” Fos-LI appearing during the development of polyarthritis in the absence of any intentional stimulation. We showed that: (1) Fos-LI evoked by ankle stimulation was not modified by either aspirin (150 mg/kg i.v.) or proacetaminophen (300 mg/kg i.v.) injection or by a 10-day chronic treatment with acetaminophen (250 or 500 mg/kg/day). (2) Despite the fact that the clinical signs of arthritis were reduced, basal Fos-LI induced by AIA disease was not changed after a 2-week chronic treatment with either aspirin (300 mg/kg/day) or acetaminophen (500 mg/kg/day) starting 3 weeks after AIA inoculation i.e., at the maximal stage of hyperalgesia and when Fos-LI is maximal. This observation questions the suitability of Fos-LI technique to gauge the effects of mild analgesics. (3) In contrast, when the same chronic treatment was applied during the development of AIA i.e., 1 week after inoculation, the number of Fos-LI nuclei was significantly decreased (about 50%) in aspirin- and acetaminophen-treated groups as compared to vehicle-treated groups. In parallel, the clinical signs of AIA disease were blocked by the two drug treatments. In addition, 2 weeks after the end of treatment, neither the clinical signs nor the number of Fos-LI increased again. The fact that the two drugs are able to prevent c- fos expression during development of arthritis, but not to interfere with already existing c- fos expression, suggests that for pharmacological investigations this technique should be used with caution. Thus, the potential use of Fos-LI to gauge the effects of non-steroidal antinociceptive drugs and other mild analgesics during chronic disease such as arthritis is discussed.

Induction of arthritis in monkeys by immunization with type II collagen.

Immunization of two cynomolugus and three rhesus monkeys with purified type II collagen resulted in the development of polyarthritis. Arthritis first became clinically apparent 7 wk after primary immunization and persisted for 16 mo. Radiologic examination of the limbs demonstrated soft tissue swelling with severe joint destruction including loss of cartilage and bone. Involved joints eventually became ankylosed with permanent loss of some motion. All of the monkeys developed a response to the immunizing collagen as determined by ELISA of serum for antibodies. Arthritis was associated with weight loss and constitutional symptoms, including lethargy and refusal to eat. One monkey became so debilitated that it was necessary to euthanize it. Histologic examination of the joints showed synovial hypertrophy with pannus formation. A control monkey immunized with type I collagen suffered no apparent ill effects.

Adjuvant polyarthritis and the pseudosynovitis.

The cavity lining of a six day old subcutaneous air pouch in rats resembles normal synovium in morphology and responds in a comparable manner during development of polyarthritis. The ability of newly formed pouches (one and two days old) to respond similarly to polyarthritogen was examined here. Positive macro and microscopic changes similar to those seen in the six day old pouch were observed in rats previously inoculated with adjuvant. The intensity of some of these changes varied between pouches. The results of this study indicate that the adjuvant induced air pouch reaction does not depend on the presence of synovial-like lining for its production.

Anti-peptidoglycan antibody in the rats with acute and chronic polyarthritis after multiple systemic injections of streptococcal cell wall peptidoglycans

A systemic administration of aqueous form of peptidoglycan polysaccharide polymer (PG-APS) derived from S. pyogenes induced acute and chronic form of polyarthritis in all the rat strains tested. SHR developed severe arthritis 24 hours after injection and developed very low titer of IgM and IgG antibody to PG-APS whereas WKY appeared to be resistant to polyarthritis but developed high titer of antibody to PG-APS. Congenitally athymic nude rats developed acute polyarthritis and high titer of antibody but developed chronic form of polyarthritis only after multiple injection of PG-APS whereas euthymic rnu/+ rats easily developed severe acute and chronic polyarthritis and developed relatively lower titer of antibody than rnu/rnu rats. There existed good correlation between antibody formation and acute polyarthritis among rnu/rnu and rnu/+ rats whereas no correlation existed between chronic form of polyarthritis and antibody formation.Acute exacerbation of polyarthritis occured within 24 hours after booster injection of PG-APS but no secondary antibody response were observed. It was thus considered that the pathogenesis of this polyarthritis may be different from that of adjuvantinduced arthritis where T cell may play an important role and whether or not antibody to PG-APS is associated with the development of polyarthritis.

Serum transfer of collagen-induced arthritis in mice.

Immunization of DBA/1 mice with native chick type II collagen resulted in development of polyarthritis 4-5 wk later. Sera of these mice contained high levels of anticollagen antibodies, and immunoglobulin concentrates of their sera transferred arthritis to unimmunized recipients. Histopathologically, this passively transferred arthritis resembled the early disease of immunized donors. Immunofluorescence studies demonstrated the deposition of IgG and C3 on the articular surface but not in synovial tissue of arthritic joints. Transferred, isotopically labeled anticollagen antibodies rapidly localized to the limbs and to other cartilage-containing tissues. When transfer concentrate was administered to arthritis-resistant strains, they also developed arthritis. Indeed, immunoglobulin concentrates from rats with collagen-induced arthritis transferred arthritis to naive mice. The amount of concentrate required for transfer to B10.D2 resistant mice was reduced by immunizing them with collagen 4 wk before transfer. Although susceptibility to arthritis from immunization is H-2 linked, these studies clearly demonstrate that passive transfer of arthritis depends upon injection of specific antibody and not on other host factors.

Changes of peritoneal mast-cell population in rats with adjuvant arthritis

Adjuvant was injected into the left hind paw of Sprague-Dawley rats. A marked decrease in the mast-cell count and histamine content of the peritoneal fluid and a significant increase in the histamine content as well as the mast-cell count in the mesentery appeared between 1 and 2 weeks after adjuvant injection. This period approximately coincided with that of the development of secondary inflammatory lesions such as polyarthritis. The effects of some antiinflammatory and immunosuppressive drugs on the decrease in the mast-cell count and histamine content of peritoneal fluid were studied as well as the effect on the development of polyarthritis. With the exception of flufenamic acid, the preventive effects on the decrease in the peritoneal mast-cell count paralleled the prevention of development of arthritic lesions.These results show that the redistribution of mast cells between the peritoneal cavity and the tissues surrounding it is one of the symptoms of ‘adjuvant disease’ which results from delayed hypersensitivity.