Chihiro Murai

Spontaneous Occurrence of Anti-Fibrillin-1 Autoantibodies in Tight-Skin Mice

Tight-skin (TSK) mouse represents an experimental for systemic sclerosis, displaying cutaneous hyperplasia, connective tissue alterations in the internal organs and developing autoantibodies against several scleroderma target autoantigens. TSK mouse syndrome is associated with a mutation in fibrillin-1 (Fbn-1), the major component of 10 nm microfibrils. Here, we have investigated whether TSK mouse develops autoimmunity to Fbn-1 similar to scleroderma target autoantigens. Our results show that anti-Fbn-1 IgG autoantibodies are present in high titer in many TSK mice. Specificity of these antibodies was confirmed by competitive inhibition assays and Western blotting analysis using recombinant human Fbn-1 protein. TSK mouse autoantibodies recognize a conserved epitope present in the C region of Fbn-1. These results indicate the presence of Fbn-1 specific T and B cells in TSK mouse repertoire.

Rheumatoid arthritis after human parvovirus B19 infection

Polyarthropathy associated with human parvovirus B19 (B19) is usually transient, but often resembles rheumatoid arthritis (RA).1-3 However, B19 DNA screened by polymerase chain reaction (PCR) may be positive not only in autoimmune diseases, but also in non-arthropathy.4 To study whether or not RA occurs after acute B19 infection, we conducted a prospective study of patients with acute onset polyarthritis. Sixty seven cases showing acute inflammatory polyarthritis from January 1990 to June 1990 were examined and followed up for six years. Among them, 12 (9 female and 3 male) exhibited IgM anti-B19 antibodies.5 PCR, followed by a Southern blot analysis6 also showed the presence of B19 DNA in all 12 cases with IgM anti-B19 antibodies, but did not in the remainder. Initially, rheumatoid factor (RF) was negative in all B19 positive cases except one, but became positive in four, two to four months after the infection (table 1). Among RF …

The frequency of human parvovirus B19 infection in nonimmune hydrops fetalis

Intrauterine infection of human parvovirus B19 has recently been identified as an etiology for nonimmune hydrops fetalis (NIHF) and fetal death. To examine the frequency of B19 infection in cases of NIHF, forty two cases of NIHF of unknown cause were tested for the presence of B19 antibodies by enzyme-linked immunosorbent assay (ELISA) and B19 DNA by polymerase chain reaction (PCR). Three maternal sera were positive for B19 IgM antibody and one fetal serum was positive for B19 DNA. Overall, four (10%) of the 42 cases were positive for B19 infection. All of the four cases positive for B19 infection were found during or just before an outbreak of erythema infectiosum and the incidence was calculated at 36% if only cases found during the outbreak were collected. In all four cases of B19 infection, NIHF was diagnosed at 20 to 23 weeks of gestation, which suggested that B19 infection might be a particular threat to the fetus during this stage of gestation. In conclusion, B19 infection may contribute to 10% of cause unknown NIHF and the incidence may be higher if cases during outbreaks are exclusively collected.

Human parvovirus B19 in rheumatoid arthritis.

Viral arthritis occurs transiently in most cases, because the infection is self limiting. The arthropathy associated with human parvovirus B19, however, often lasts for more than 2 years and their clinical symptoms may resemble with those of rheumatoid arthritis. Data have been accumulating for the link of B19 infection with chronic polyarthropathy or rheumatoid arthritis (RA), and we discuss the possible mechanism for the role of B19 in the etiopathology of RA.

Clinical and structural remission rates increased annually and radiographic progression was continuously inhibited during a 3-year administration of tocilizumab in patients with rheumatoid arthritis: A multi-center, prospective cohort study by the Michinoku Tocilizumab Study Group

Abstract Objective: To evaluate the clinical and structural efficacy of tocilizumab (TCZ) during its long-term administration in patients with rheumatoid arthritis (RA). Methods: In total, 693 patients with RA who started TCZ therapy were followed for 3 years. Clinical efficacy was evaluated by DAS28-ESR and Boolean remission rates in 544 patients. Joint damage was assessed by calculating the modified total Sharp score (mTSS) in 50 patients. Results: When the reason for discontinuation was limited to inadequate response or adverse events, the 1-, 2-, and 3-year continuation rates were 84.0%, 76.8%, and 72.2%, respectively. The mean DAS28-ESR was initially 5.1 and decreased to 2.5 at 6 months and to 2.2 at 36 months. The Boolean remission rate was initially 0.9% and increased to 21.7% at 6 months and to 32.2% at 36 months. The structural remission rates (ΔmTSS/year ≤ 0.5) were 68.8%, 78.6%, and 88.9% within the first, second, and third years, respectively. The structural remission rate at 3 years (ΔmTSS ≤ 1.5) was 66.0%, and earlier achievement of swollen joint count (SJC) of 1 or less resulted in better outcomes. Conclusions: TCZ was highly efficacious, and bone destruction was strongly prevented. SJC was an easy-to-use indicator of joint destruction.

Is Methotrexate (MTX) Necessary in Combination Therapy with Tocilizumab and MTX for Rheumatoid Arthritis in Remission? Cohort Study Carried by the Michinoku Tocilizumab Study Group

Objectives: To determine the necessity of methotrexate (MTX) in patients with rheumatoid arthritis (RA) achieving clinical remission treated by tocilizumab (TCZ) and MTX (TCZ+MTX). Methods: A 3 year, multicenter, observational cohort study was performed. RA patients were treated by TCZ with or without MTX depending on the attending doctor’s decision. Of the patients treated with TCZ+MTX, the patients who discontinued MTX after achieving clinical remission (discontinued group: DISC) were compared with those who maintained the same dose of MTX after achieving clinical remission (maintained group: MAIN). Results: The DISC and MAIN consisted of 33 patients and 37 patients, respectively. The mean DAS28-ESR was significantly lower in the DISC than in the MAIN at 3 months, 6 months and 9 months (3 months: 1.8 ± 0.8 and 2.4 ± 1.0, p=0.018, 6 months: 1.5 ± 0.7 and 2.2 ± 1.0, p=0.009 and 9 months: 1.4 ± 0.6 and 2.0 ± 1.0, p=0.008, respectively). The DAS28-ESR remission rate and Boolean remission rate were significantly higher in the DISC than in the MAIN (93.8% and 64.5%, respectively in the DAS28-RSR, p=0.04; 51.6% and 17.2%, respectively in the Boolean, p=0.005) at 6 months. Conclusions: RA patients treated by the combination of TCZ and MTX who achieved deep remission (DAS28- ESR ≤ 1.98) at as early as 3 months could discontinue taking MTX.

The Role of Exogenous Stimulation in Pathogenesis of Autoimmune Diseases

A properly operating immune system enables the body to maintain a healthy status quo by distinguishing between the antigens associated with the organism itself, which are allowed to persist, and the antigens borne by foreign molecules, which are disposed. Burnet (1). proposed that the ability of immune system to distinguish “self and nonself ‘antigens results from the elimination of self-reactive lymphocytes during ontogenic development. This concept is supported by recent data originating from studies carried out in transgenic mice demonstrating that self-reactive T- and B- lymphocytes are deleted from the repertoire. In the thymus, a process known as negative selection appears to result in deletion of T-cells bearing receptors with high affinity for self-antigens (2,3). In the fetal liver and bone marrow, a similar process deletes the emerging B-cells bearing an Ig receptor specific for cellular antigens (4).