Clinical and serological associations of ribosomal P autoantibodies in systemic lupus erythematosus: prospective evaluation in a large cohort of Italian patients: reply

R. Gerli and L. Caponi1,

University of Perugia, Center for the Study of Rheumatic Diseases, Section of Internal Medicine & Oncological Sciences, Department of Experimental & Clinical Medicine, Perugia, PG and
1 University of Pisa, Laboratory of Specialised Clinical Analysis, Department of Experimental Pathology BMIE, Pisa, PI, Italy

SIR, We thank Drs Cuchacovich and Espinoza for their letter that strongly supports our data on clinical and serological associations of anti-P antibodies in patients with systemic lupus erythematosus [1]. Of particular interest is the confirmation of the association between anti-P and anti-phospholipid antibodies, which has been reported only sporadically in the past [2, 3]. Moreover, it is intriguing that in the patient group studied by Cuchacovich, as in ours, no correlation between the presence of anti-P and clinical evidence of anti-phospholipid syndrome was found.

We agree that the explanation for such an association is yet to be elucidated. In our opinion, however, cross-reactivity cannot be completely ruled out. The association between different antibody specificities in the same serum is often suggestive evidence, but it should be verified with dedicated experiments where specific antibodies are purified and tested on specific substrates. If purified antibodies show no reactivity to antigens other than those used in the purification procedure, it is reasonable to conclude that cross-reactivity does not exist. Otherwise, if a binding ability appears, the antibody specificity must be tested with inhibition experiments that are able to verify the capacity of a certain antigen to hinder the binding towards the other(s).

In our opinion, this is the best way to finely evaluate the binding ability of spontaneously developed autoantibodies and to provide some hints to clarify their specificity. On the other hand, however, the demonstration in our study that anti-P and anti-cardiolipin antibodies were associated, but their serum levels were not strictly correlated [1], may argue against a cross-reactivity of these two autoantibodies. This observation may suggest that, in fact, the autoimmune response against ribosomal P proteins and cardiolipin in lupus patients may be evoked through a common pathogenic pathway, but that the trigger agents able to elicit and enhance autoantibody response may be quite different. In this setting, it is conceivable that infectious agents, including viruses, bacteria or parasites, may play a key role in triggering these autoimmune responses, as Cuchacovich and Espinoza suggest. We also think, however, that further, more detailed studies may help to clarify the possible pathogenic involvement of either P0 protein, which may be expressed on the surface of a number of cells, including endothelium [47], or apoptotic blebs, which are able to externalize nuclear and cytoplasm structures, such as ribosome proteins [811].

Notes

Correspondence to: R. Gerli. E-mail: gerlir{at}unipg.it Back

References

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  2. Schneebaum AB, Singleton JD, Sterling GW at al. Association of psychiatric manifestation with antibodies to ribosomal P proteins in systemic lupus erythematosus. Am J Med 1991;90:54–62.[ISI][Medline]
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Accepted 8 January 2002





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