Article Text


A unique autoantibody pattern of positive anti-Jo-1, anti-U1RNP, and antiproteasome antibodies in autoimmune myositis as a diagnostic challenge
  1. E Feist1,
  2. M-L Schneider2,
  3. M Brychcy1,
  4. T Dörner1,
  5. G-R Burmester1,
  6. F Hiepe1
  1. 1Clinic for Rheumatology and Clinical Immunology, University Hospital Charité, Humboldt University of Berlin, Schumannstr 20/ 21, D-10117 Berlin, Germany
  2. 2Clinic for Gastroenterology, Hepatology and Endocrinology, University Hospital Charité
  1. Correspondence to:
    Dr E Feist;

Statistics from

The presence of autoantibodies against tRNA synthetases is a specific serological feature of a clinically distinct entity of autoimmune myositis. This syndrome is characterised by an association of non-erosive arthritis, Raynaud’s phenomenon, and alveolitis. The most common autoimmune response of this disease is directed against the histidyl-tRNA synthetase Jo-1 and therefore also called the anti-Jo-1 syndrome.1–3 In this report we describe a patient with a unique coincidence of anti-Jo-1 antibodies with other myositis related autoantibodies directed to U1RNP typical for mixed connective tissue disease (MCTD) and proteasome.


In a 36 year old female patient, arthralgia, joint swelling, and fever led to the diagnosis of rheumatoid arthritis in 1998. Initial treatment comprised sulfasalazine and prednisolone. In February 2000, she was admitted to our department with a four month history of myalgia and weakness. Physical examination showed a tetraparesis affecting the proximal and peripheral muscles with an apparent areflexia. Gottron’s sign was positive, while arthritis was not evident. A marked pathological spontaneous activity of all muscle groups was found on electrophysiological examination. Pulmonary function tests and thoracic x ray results were normal.

Autoantibody analysis showed an antinuclear antibody titre of 1/2560 with a pattern suspicious for a coincidence of anti-U1RNP- and anti-Jo-1 antibodies (fig 1A). Enzyme linked immunosorbent assay (ELISA) and immunoblotting confirmed the reactivity against RNP-A and B/B′ as well as Jo-1 (fig 1B). Moreover, antiproteasomal autoantibodies were detectable in ELISA, while other autoantibodies were negative. The antiproteasome antibodies were affinity purified by means of 20S proteasome bound to BrCN-sepharose and subsequently tested in immunofluorescence (fig 1C). Circulating immune complexes were found to be raised and complement components C3 and C4 were decreased. Creatinine kinase (2579 U/l, normal 0–80), myoglobin (1942 μg/l, normal 0–70), lactate dehydrogenase, and transaminases were strongly enhanced. Other laboratory data were normal, including peripheral blood count, C reactive protein, renal and thyroid function tests. A muscle biopsy from the right quadriceps showed a strong perivascular and endomysial infiltration, predominantly by cytotoxic T lymphocytes (CD8+) and B lymphocytes (CD20+).

Figure 1

(A) Indirect immunofluorescence of the patient’s serum showed a coarse granular nucleoplasmic pattern as well as fine speckled cytoplasmic staining in interphase HEp-2 cells. (B) Reactivity towards U1RNP antigens (A and B/B′) and histidyl-tRNA synthetase (Jo-1) was confirmed by immunoblot (lane 2), which was performed as described previously using a MOLT-4 cell extract.9 Lanes 1 and 3 represent control sera recognising Jo-1 and Sm/U1RNP antigens, respectively. (C) Affinity purified antiproteasome antibodies showed a fine speckled cytoplasmic and nucleoplasmic staining on HEp-2 cells, which was not clearly distinguishable from the immunofluorescence pattern of anti-Jo-1 antibodies.

The overall findings were consistent with a severe autoimmune myositis without any evidence of an infectious, malignant, or endocrine cause. The likelihood of sulfasalazine induced autoantibodies and disease was low, because the autoantibody response was specific and the disease continued after withdrawal of the drug. Therefore, treatment was started with steroids (initially 750 mg methylprednisolone), leading to a rapid clinical improvement. Furthermore, monthly infusions of immunoglobulins (25 g over five days) were given. Because after a period of six months (prednisolone 12 mg/day) a flare recurred, another steroid bolus of 750 mg methylprednisolone in combination with intravenous cyclophosphamide was given, leading to an improvement of all clinical symptoms. In the follow up, the course of the disease remains stable.


During the past decades, detection of autoantibodies has improved remarkably the diagnosis of connective tissue diseases and provided new insights into their pathogenesis. Inthis case, the simultaneous occurrence of anti-Jo-1 and anti-U1RNP autoantibodies is a difficult diagnostic problem. Autoantibodies against Jo-1 are usually highly specific for the anti-synthetase syndrome.1 However, in this case, the manifestation was incomplete, lacking pulmonary and peripheral vascular involvement. On the other hand, anti-U1RNP antibodies are a serological marker for MCTD, in which myositis is not an essential part but a typical symptom.2 However, the titre of the anti-U1RNP antibodies was not as high as it is typically for MCTD. The finding of low complement levels is not typical for myositis and might have been due to overlap of myositis with MCTD as complement factors can be decreased, especially in MCTD. Although an association between anti-Jo-1 and anti-Ro/SSA 52 kDa responses is relatively common, as reported by former studies,4–6 the coincidence of anti-Jo-1 and anti-U1RNP antibodies appears to be less common.3 Autoantibodies against proteasome were recently found in association with autoimmune myositis and other connective tissue diseases.7,8 In this case, the unique autoantibody pattern detected impressively reflects the variability of these myositis related markers and emphasises that they belong to the common immune repertoire seen in autoimmune myositis.


View Abstract

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.