Atypical ANCA pattern with simultaneous presence of MPO and PR3-ANCA in systemic lupus erythematosus
S Chhabra1, RW Minz1, L Goyal1, S Singh2,
1 Department of Immunopathology, PGIMER, Chandigarh, India
2 Department of Internal Medicine, PGIMER, Chandigarh, India
Department of Immunopathology, PGIMER, Chandigarh
|How to cite this article:|
Chhabra S, Minz R W, Goyal L, Singh S. Atypical ANCA pattern with simultaneous presence of MPO and PR3-ANCA in systemic lupus erythematosus.J Postgrad Med 2010;56:217-218
|How to cite this URL:|
Chhabra S, Minz R W, Goyal L, Singh S. Atypical ANCA pattern with simultaneous presence of MPO and PR3-ANCA in systemic lupus erythematosus. J Postgrad Med [serial online] 2010 [cited 2022 Aug 16 ];56:217-218
Available from: https://www.jpgmonline.com/text.asp?2010/56/3/217/68636
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. 
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.  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.  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.  Savige et al., showed occurrence of atypical ANCA among SLE patients with antigenic specificities to cathepsin G and lactoferrin. 
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.  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. 
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.
|1||Molnar K, Kovacs L, Kiss M, Husz S, Dobozy A, Pokoerny G. Anti-neutrophil cytoplasmic antibodies in patients with systemic lupus erythematosus. Clin Exp Dermatol 2002;27:56-61.|
|2||Savige J, Gillis D, Benson E, Davies D, Esnault V, Falk RJ, et al. International consensus statement on testing and reporting of antineutrophil cytoplasmic antibodies (ANCA). Am J Clin Pathol 1999;111:507-13.|
|3||Wilk A, Rasmussen N, Wieslander J. Methods to detect autoantibodies to neutrophilic granulocytes. Manual of biological markers of disease. Amsterdam: Kluwer academic publishers; 1993. p. 1-14.|
|4||Pradhan VD, Badakere, Bichile LS, Almeida AF. Anti-neutrophil cytoplasmic antibodies (ANCA) in systemic lupus erythematosus: Prevalence, clinical associations and correlation with other autoantibodies. J Assoc Physicians India 2004;52:533-7.|
|5||Savige JA, Chang L, Wilson D, Buchanan RR. Autoantibodies and target antigens in anti-neutrphil cytoplasmic antibody (ANCA) associated vasculitis. Rheumatol Int 1996;16:9-14. |
|6||Savige J, Dimech W, Fritzler M, Goeken J, Hagen EC, Jennette JC, et al. Addendum to the international consensus statement on testing and reporting of antineutrophil cytoplasmic antibodies: Quality control guidelines, comments, and recommendations for testing in other autoimmune diseases. Am J Clin Pathol 2003;120:312-8.|
|7||Jethwa HS, Nachman PH, Flak RJ, Jennette JC. False-positive myeloperoxidase binding activity due to DNA/anti-DNA antibody complexes: A source for analytical error in serologic evaluation of anti-neutrophil cytoplasmic autoantibodies. Clin Exp Immunol 2000;121:544-50.|