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Journal of Postgraduate Medicine, Vol. 56, No. 3, July-September, 2010, pp. 217-218 Case Snippet Atypical ANCA pattern with simultaneous presence of MPO and PR3-ANCA in systemic lupus erythematosus Chhabra S, Minz RW, Goyal L, Singh S1 Departments of Immunopathology and 1 Internal Medicine, PGIMER, Chandigarh, India Correspondence Address: Dr. Seema Chhabra, Department of Immunopathology, PGIMER, Chandigarh, India, drseemachhabra@rediffmail.com Code Number: jp10061 PMID: 20739771 DOI: 10.4103/0022-3859.68636 Coexistence of anti-neutrophil cytoplasmic antibodies (ANCA) and antinuclear antibodies (ANA) in systemic lupus erythematosus (SLE) patients is an interesting phenomenon. We report a rare case of SLE that showed atypical ANCA pattern on indirect immunofluorescence (IIF) with dual specificity for myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA. A 26-year-old female presented in the emergency with severe breathlessness that gradually progressed over six months. Her past history revealed-swelling, redness and pain in the small joints of the hands, shoulder and elbow and features of Raynaud's phenomenon suggesting musculoskeletal involvement. She also gave a history of herpes labialis two years ago. She had an episode of seizures three years back and since then she has been on antiepileptic therapy. After thorough clinical and laboratory workup she was diagnosed as active SLE with multi-organ involvement according to ACR (American College of Rheumatology) criteria. Two-D Echo showed dilated cardiomyopathy, moderate left ventricular systolic dysfunction, mitral regurgitation and global hypokinesia, with a left ventricular ejection fraction of 41%. Urine examination revealed subnephrotic range proteinuria with 24-h urinary protein value of 576 mg/24 h. Hematological workup revealed hemolytic anemia, thrombocytopenia and leukopenia. Autoimmune workup revealed 4+ homogeneous pattern of antinuclear antibody (ANA) on Human epithelioma cell line (Hep2). The enzyme-linked immunosorbent assay (ELISA) for dsDNA (VARELISA) was highly positive. IIF for ANCA on ethanol-fixed neutrophil preparation showed atypical ANCA pattern with both nuclear and cytoplasmic fluorescence. ELISA for PR3-ANCA (VARELISA) and MPO-ANCA (VARELISA) were also highly positive suggesting dual ANCA antigenic specificity. All ELISAs were put in duplicate. Serum C 3 and C 4 levels were decreased. By IIF, the prevalence of ANCA in SLE patients has been reported in the range of 3-69% and the majority of patients have shown P-ANCA pattern. [1] Diffuse ANA positivity in SLE patients mimics a typical P-ANCA or atypical ANCA pattern, however it is MPO or PR3-negative on ELISA. To confirm dual positivity of ANA/ANCA, PR3 and MPO ELISAs are essential. [2] Atypical ANCA pattern (snow drift pattern) is granulocyte and monocyte-specific, interpreted as a combination of nuclear and cytoplasmic fluorescence and is difficult to interpret on IIF, more so in this particular case due to 4+ diffuse ANA positivity. Sometimes lymphocytes in the neutrophil preparations may help to improve ANCA interpretation in the presence of ANA as neutrophils but not lymphocytes contain MPO. [3] ELISAs are, however, mandatory in such situations with ANCA vs. ANA or simultaneous positivity for both. Atypical ANCA pattern in two SLE patients has also been previously reported by Pradhan et al., that also showed dual MPO and PR3-ANCA specificities. [4] Savige et al., showed occurrence of atypical ANCA among SLE patients with antigenic specificities to cathepsin G and lactoferrin. [5] The international consensus statement on testing and reporting of antineutrophil cytoplasmic antibodies also reports an "atypical ANCA positive pattern with PR3-ANCA negative or 1+ and MPO-ANCA negative or 1+". This result occurs in inflammatory bowel disease and other autoimmune diseases where its clinical significance is unclear. It does not occur in Wegener's granulomatosis, microscopic polyangiitis (and its renal-limited variant), or Churg-Strauss syndrome. [6] Jethwa et al., suggest that the DNA contained within the antigen-binding site of anti-DNA antibodies could bind to the highly cationic MPO used as substrate antigen in immunoassays, resulting in a false-positive test. [7] The present case has been reported here due to the rarity of finding an atypical ANCA pattern among SLE patients, that too with dual antigenic specificity. Whether the presence of atypical ANCA in lupus patients is a mere epiphenomenon or forms a subset of lupus patients who will have more extensive vasculitis will need to be worked out in larger cohorts. References
Copyright 2010 - Journal of Postgraduate Medicine |
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