Human Chondrocyte Activation by Toxins From Premolis semirufa, an Amazon Rainforest Moth Caterpillar: Identifying an Osteoarthritis Signature.

Pararamosis is a disease that occurs due to contact with the hairs of the larval stage of the Brazilian moth Premolis semirufa. Envenomation induces osteoarticular alterations with cartilage impairment that resembles joint synovitis. Thus, the toxic venom present in the caterpillar hairs interferes with the phenotype of the cells present in the joints, resulting in inflammation and promoting tissue injury. Therefore, to address the inflammatory mechanisms triggered by envenomation, we studied the effects of P. semirufa hair extract on human chondrocytes. We have selected for the investigation, cytokines, chemokines, matrix metalloproteinases (MMPs), complement components, eicosanoids, and extracellular matrix (ECM) components related to OA and RA. In addition, for measuring protein-coding mRNAs of some molecules associated with osteoarthritis (OA) and rheumatoid arthritis (RA), reverse transcription (RT) was performed followed by quantitative real-time PCR (RT-qPCR) and we performed the RNA-sequencing (RNA-seq) analysis of the chondrocytes transcriptome. In the supernatant of cell cultures treated with the extract, we observed increased IL-6, IL-8, MCP-1, prostaglandin E2, metalloproteinases (MMP-1, MMP-2, MMP-3 and MMP-13), and complement system components (C3, C4, and C5). We noticed a significant decrease in both aggrecan and type II collagen and an increase in HMGB1 protein in chondrocytes after extract treatment. RNA-seq analysis of the chondrocyte transcriptome allowed us to identify important pathways related to the inflammatory process of the disease, such as the inflammatory response, chemotaxis of immune cells and extracellular matrix (ECM) remodeling. Thus, these results suggest that components of Premolis semirufa hair have strong inflammatory potential and are able to induce cartilage degradation and ECM remodeling, promoting a disease with an osteoarthritis signature. Modulation of the signaling pathways that were identified as being involved in this pathology may be a promising approach to develop new therapeutic strategies for the control of pararamosis and other inflammatory joint diseases.

Anti-alpha-enolase antibodies in Behçet's disease: a marker of mucocutaneous and articular disease activity?

OBJECTIVES: To assess IgM anti-alpha-enolase antibodies (AAEA) in systemic Behçet's disease (BD) and its possible association with clinical manifestations and disease activity. METHODS: Ninety-seven consecutively selected BD patients were compared to 36 enteropathic spondyloarthritis (ESpA) [24 Crohn's disease (CD) and 12 ulcerative colitis (UC)] patients and 87 healthy controls. IgM AAEA was detected by immunoblotting. Disease activity was assessed by standardised indexes, Brazilian BD Current Activity Form (BR-BDCAF) for BD and Harvey-Bradshaw Index (HBI) for CD and UC patients. A second evaluation was performed in BD patients (n=56), regarding IgM AAEA presence, disease activity scores and C-reactive protein (CRP). RESULTS: Higher IgM AAEA prevalence was found in 97 BD (17.7%) compared to ESpA (2.8%) and healthy controls (2.3%), p<0.001. IgM AAEA frequency was higher in active BD compared to inactive BD (30.2% vs. 7.4%, p=0.006), a finding confirmed in the second cross-sectional evaluation of 56 of these BD patients (45.5% vs. 13.3%, p=0.02). Mean BR-BDCAF scores were higher in IgM AAEA positive group on both evaluations (9.1 ± 5.4 vs. 4.9 ± 4.9, p=0.002; 5.0 ± 4.9 vs. 2.2 ± 2.9, p=0.01, respectively). BD patients with mucocutaneous and articular symptoms presented higher IgM AAEA positivity in the first and second evaluations (64.7% vs. 27.5%, p=0.005; 36.4% vs. 7.1%, p=0.039 respectively). CONCLUSIONS: Our data support the notion that alpha-enolase is a target antigen in BD, particularly associated with disease activity, mucocutaneous and articular involvement. In addition, IgM AAEA may distinguish BD from ESpA, especially in patients with high disease activity.

Association of CXCL13 serum level and ultrasonographic findings of joints in patients with systemic lupus erythematosus and Jaccoud's arthropathy.

Objectives The objective of this paper is to perform an ultrasonography (US) analysis of hands and wrists in two groups of patients with systemic lupus erythematosus (SLE), with and without Jaccoud's arthropathy, matched by age and disease duration and to correlate them with levels of CXCL13 clinical features, laboratory tests and disease activity score. Methods Sixty-four patients with SLE were enrolled, 32 with and 32 without Jaccoud's arthropathy. Each patient underwent physical examination, laboratory tests (including CXCL13 by ELISA) and bilateral US. Synovial hypertrophy, tenosynovitis and erosions were evaluated according to a semiquantitative grading system with a 0-3 rating. US findings were correlated with serum levels of CXCL13, other serological parameters and disease activity index. Results Synovitis was found in 25/64 patients (39%) and tenosynovitis in 14/64 (22%). These findings were more frequent in SLE patients with Jaccoud's arthropathy, particularly tenosynovitis ( p = 0.002) and synovitis ( p = 0.01). Median serum level of CXCL13 was 20.16 pg/ml in the whole population (23.21 pg/ml in the Jaccoud's arthropathy group and 11.48 pg/ml in the group without). There was an association between the presence of disease activity and high level of CXCL13 ( p = 0.004). However, no association was found between high levels of CXCL13 and "arthritis" in SLEDAI, swollen joints on physical examination or synovitis on US. Conclusions US findings in joints of SLE patients with Jaccoud's arthropathy confirm that synovitis and tenosynovitis are common in these patients. In addition, serum level of CXCL13 is associated with disease activity in SLE but does not seem to be a biomarker for arthritis in these patients.

Acute arthropathy in patients with rash diseases: a comparative study.

The aim of this study was to assess the association of acute arthropathy and selected clinical features in patients with acute rash diseases. Serum samples from 1,554 patients were tested for anti-measles, dengue, human parvovirus B19, and rubella virus IgM using enzyme immunoassay. Sera from children, in whom these infections were excluded, were studied for anti-human herpesvirus type 6 IgG antibodies using an indirect immunofluorescence test. Joint complaints occurred in 31.2% of the 862 patients with an etiologic diagnosis and were more frequently seen in adults than in children (OR 8.5). Among the adults, arthropathy prevailed in women compared to men (OR 1.8). Arthropathy was most frequently reported in rubella (41.2%) and in dengue fever cases (41.1%) than in the other rash diseases studied (p < 0.0001). Joint complaints were more frequently seen in patients with fever (OR 1.6) and with five or more days of onset of the disease (OR 1.6), regardless of serological diagnosis. Arthropathy appeared as a frequent condition in rash diseases, typically with low severity and no specific pattern of joint involvement.

HLA-DRB1 alleles associated with susceptibility or resistance to rheumatoid arthritis, articular deformities, and disability in Mexican Americans.

OBJECTIVE: To study the genetics (HLA-DRB1 allele associations) of rheumatoid arthritis (RA) susceptibility and severity among Mexican Americans, an important, but understudied, US population. METHODS: HLA-DRB1 alleles were compared between 141 Mexican American patients with RA and 54 unrelated Mexican Americans without RA, and the association of these alleles with articular deformities and disability was examined. HLA-DRB1 alleles were typed using polymerase chain reaction-sequence-specific primer amplification and were classified according to the 1996 World Health Organization nomenclature. RESULTS: Of the 141 patients, 105 (74%) had at least 1 copy of the shared epitope (SE) sequence, compared with 29 (54%) of the 54 controls (P = 0.007). A significant gene-dose effect was observed, with 31 patients (22%) being homozygous for the SE compared with 1 (2%) of the controls (P = 0.004). In terms of disease severity, only 3% of RA patients who were "null" for the SE were outliers in the rate of development of articular deformities, compared with 10% of heterozygotes and 27% of homozygotes (P = 0.002). Patients who were DRB1*08 positive had significantly fewer deformities per year of disease and a slower rate of development of disability than did patients with other DRB1 alleles. CONCLUSION: HLA-DRB1 alleles containing the SE are associated with susceptibility to RA in Mexican Americans, and may also be associated with a more rapid development of articular deformities and disability. HLA-DRB1*08 appears to have a protective influence on RA susceptibility and disease severity in Mexican Americans.

Tarsitis anquilosante

La tarsitis anquilosante en una entidad recientemente descrita, perteneciente al grupo de las espondiloartropatías seronegativas relacionadas con el HLA-B27, la cual puede hacer parte de la espondilitis anquilosante o presentarse como una condición aislada. Presentamos el caso de una mujer de 25 años con historia conocida de 11 años de evolución con un cuadro clínico característico de la enfermedad, siendo el primer caso informado en Colombia. Se describe además la técnica de Harris, como un método radiológico simple de ayuda para el diagnóstico de la entidad

Deforming arthropathy of the hands in systemic lupus erythematosus.

Forty-one of 858 patients with systemic lupus erythematosus (SLE) developed clinical deformity of their hands. This deformity was clinically and radiologically different from that found in 40 patients with classical or definite rheumatoid arthritis (RA), and tended to appear early in the course of disease. Characteristics of this arthropathy included nonerosive carpal collapse; exceptional erosion of the styloid processes; Z deformity of the thumb; nonerosive ulnar deviation and subluxation of MCP joints; parametacarpophalangeal joint hook formation; scant and asymmetric joint erosions; and swan neck deformity of the fingers. Most of these changes seemed to be due to involvement of the ligaments rather than to the destructive effect of synovitis. Patients with SLE with deforming arthropathy had a higher frequency of rheumatoid factor positivity, sicca symptoms and antibodies to native DNA, whereas they had lower incidence of facial rash and photosensitivity than did those without. Other manifestations did not differ. We propose that most patients with SLE with deforming arthropathy belong to a subset of SLE rather than representing the coexistence of SLE and RA.

Sistema H.L.A y enfermedades articulares / HLA system and joint diseases

Las asociaciones entre los antígenos del sistema HLA y las enfermedades reumatológicas se refieren especialmente al antígeno HLA-B27 el que está fuertemente ligado a la espondiloartritis anquilosante: al síndrome de Fiessinger-Leroy-Reiter; a las artritis reactivas y a los reumatismos axiales de las enterocolonopatías inflamatorias crónicas y de la psoriasis. Existen igualmente, correlaciones entre otros antígenos HLA y el reumatismo psoriásico periférico; la artritis reumatoidea del adulto y del niño; el síndrome de Gougerot-Sjögren y la enfermedad de Behcet. Las proyecciones prácticas, diagnósticas y pronósticas, de estas alteraciones se analizan y comentan

Aspectos imunológicos do complemento e fraçåo C'2 em cåes com artropatia experimental / Imunologic aspects of total complement and fraction C'2 in dogs having experimental arthropathy

Os autores estudaram o estabelecimento da artropatia em cåes, a partir do preparo de uma imunoglobulina antisinovial em coelhos. A imunoglobulina purificada e esterilizada foi usada em articulaçÆes de cåes sadios. O sangue destes animais foi colhido antes das inoculaçÆes, servindo como controle normal. Um esquema de inoculaçÆes foi estabalecido. A cada nova inoculaçåo os cåes foram sangrados e de seus sangues dosados o complemento total e a fraçåo C'2. A dosagem do complemento total foi feita de acordo com o método gráfico, retificado segundo a equaçåo de von KROGH e a fraçåo C'2, segundo o método de BORSOS, RAPP & MAYER (1961). Os animais com lesÆes artropáticas estabelecidas foram estudados radiológica e histologicamente. As lesÆes apresentaram rarefaçåo óssea e destruiçåo tecidual evidente. O nível do complemento total e da fraçåo C'2 nåo foi estatisticamente diferente do controle

Reactions to rubella vaccine and persistence of antibody in virgin-soil populations after vaccination and wild-virus-induced immunization.

Vaccination of two virgin-soil (without historical or serological evidence of past infection) populations of Amazon Indians with RA 27/3 rubella vaccine was followed by fever of greater than 100 F in 10% of the vacinees and by ephermeral arthralgia in 2%. These frequencies are not greater than those that have been reported for cosmopolitan populations of comparable ages. There was little or no secondary spread of the virus. Titers of hemagglutination-inhibiting antibody to rubella virus were prevalent in a third population of Amazon Indians, who had naturally acquired immunity and were unexposed to reinfection, and did not decline during a period of four to 12 years after infection. Antibody titers in the two virgin-soil populations immunized with RA 27/3 vaccine declined by twofold between four months and two and one-half years after vaccination but, at the end of that period, were not appreciably lower than antibody titers at four years in the naturally infected population. All age groups except children under one year of age responded to vaccination equally well.