Prevalence of antineutrophil cytoplasmic antibodies in a large inception cohort of patients with connective tissue disease

Authors: Merkel P, Polisson R, Chang Y, Skates S, Niles J.
Source: Annals of Internal Medicine. 126:866-73. June 1, 1997.
Institution: Harvard Medical School.
Financial support: None indicated.

Summary

Background

Antineutrophil cytoplasmic antibodies (ANCA) are associated with a number of vasculitides, including Wegener granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis and idiopathic necrotizing and crescentic glomerulonephritis. A number of connective tissue diseases (CTD's) present with similar findings to the vasculitides. If ANCA is specific to the vasculitic syndromes and remains negative in the CTD's, this would greatly enhance its utility. This study was designed to look at the results of several types of ANCA assays in patients with various connective tissue diseases.

Methods

Results

Authors' Discussion

The authors note that their study confirms the specificity of ANCA for the diagnosis of Wegener granulomatosis, microscopic polyangiitis and related vasculitides. However, their results also demonstrate the inadequacy of immunofluorescence alone. Much more specific results were obtained with the ELISA techniques, and the best results were obtained using a combination of immunofluorescence and ELISA.

P-ANCA immunofluorescence performed particularly poorly in patients with lupus. This appears to be due to the antinuclear antibodies which can create a P-ANCA and atypical ANCA pattern on immunofluorescence.

Although C-ANCA was highly specific and was negative in all patients with CTD in this study, many of the negative C-ANCA assays were discordant on initial analysis and only negative after a second staining. This underlines the subjectivity of the immunofluorescence method.

Comment

This study helps to clarify the utility of the ANCA assay, and it also brings home the fact that test results should not be regarded in a vacuum -- the laboratory methods used may be very important. ANCA is not equal to ANCA, as this paper makes clear. ELISA appears to be superior to immunofluorescence, and a combination of the two seems to be best of all. How many of us know what method our own laboratories use, when we order serum for ANCA?

June 10, 1997


Reader comments

Date: Sun, 29 Jun 1997
From: gurj <gurj@netten.net>

This study examining the occurence of ANCA in patients with connective tissue disease is an important one. Its clinical importance lies in when patients have early manifestations of connective tissue disease but may have aggressive organ involvement such as RPGN. One of the criticisms that the authors admit to is that the data was derived from a large study that looked at patients with UCTD. In addition, samples for the patients for anticardiolipin antibody syndrome were obtained from another laboratory. However, the results confirm other studies' findings of the high specificity for cANCA. The low specificity of pANCA is mainly due to the immunofluorescent staining by antinuclear antibodies. To improve specificity, the authors suggest that myeloperoxidase antibodies be measured by ELISA or Sandwich techniques.

Gurjit Kaeley
Rheumatology Fellow. UT, Memphis.


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References

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