LETTERS

semantic. Nevertheless, my colleagues and I have indeed performed the study suggested by BCliveau et al, in the SLE model: namely, we induced experimental SLE with Ab,- equivalent antiidiotypic antibodies (anti-anti-DNA). The in- duction of the disease was even more vigorous, and occurred sooner, than in the WG model (4). I would like to stress that the human idiotype was completely devoid of PR3. Further- more, we have recently developed a mouse anti-endothelial cell antibody (AECA) (Ab,), generated from the experimental vasculitis model (5), with which we are going to repeat our studies as we have done with the SLE model (4,6) as well as with the antiphospholipid syndrome (7,s).

Regarding the existence of mouse PR3, I would like to stress that this issue has not been settled, and the fact that human and mouse anti-PR3 do not recognize PMN PR3 does not necessarily exclude its existence. A method that is based more on biochemical principles should be utilized to confirm this. Nevertheless, even if mice lack PR3, this does not exclude the notion of Ab, (in our nomenclature) pathogenicity. My colleagues and I belong to the school that still does not believe that in systemic autoimmune diseases characterized by auto- antibodies directed against intracellular autoantigens (DNA, nucleosomes, RNP, topoisomerase MPO, PR3), the clinical manifestations are indeed the results of the binding of the autoantibody to its respective intracellular autoantigen (even if it has been shown that in some circumstances these autoanti- gens are exposed on the surface of the cells-a process I refer to as “raping immunology”) (9,lO).

I do not agree with Dr. Beliveau and colleagues regarding the greater validity of anti-MPO for this model (ll), although we are in the process of investigating it. Meanwhile, I refer the readers to an analogous model with a human polyclonal AECA, recently reported by us (1 2) .

Y. Shoenfeld, MD Sheba Medical Center Tel-Hashomer, Israel

1. Tomer Y, Gilburd B, Blank M, Lider 0, Hershkoviz R, Fishman P, Zigelman R, Meroni P-L, Wiik A, Shoenfeld Y: Characterization of biologically active antineutrophil cytoplasmic antibodies in- duced in mice: pathogenetic role in experimental vasculitis. Ar- thritis Rheum 38:1375-1381, 1995

2. Blank M, Tomer Y, Stein M, Kopolovic J, Wiik A, Meroni PL, Conforti G, Shoenfeld Y: Immunization with anti-neutrophil cytoplasmic antibody (ANCA) induces the production of mouse ANCA and perivascular lymphocyte infiltration. Clin Exp Immu- no1 102:120-130, 1995

3. Tincani A, Balesterieri G, Allegri F, Cattanco R, Fornaseri A, Li M, Sinico A, D’Amigo G: Induction of experimental SLE in naive mice by immunization with polyclonal anti-DNA antibody carrying the IVIG idiotype. Clin Exp Rheumatol 11:124-129, 1993

4. Mendlovich S, Fricke H, Shoenfeld Y, Mozes E: The role of anti-idiotypic antibodies in the induction of experimental SLE in mice. Eur J Immunol 19:729-734, 1989

5. Gilburd B, George J, Meroni PL, Youinou P, Wiik A, Shoenfeld Y: A mouse monoclonal anti-endothelial cell antibody derived from an idiotypically induced model of experimental model. Submitted for publication

6. Fricke H, Offen D, Mendlovic S, Shoenfeld Y, Bakimer R, Sperling J, Mozes E: Induction of experimental SLE in mice by immunization with a monoclonal anti-La autoantibody. Int Immu- no1 2:225-230, 1989

7.

8.

9.

10.

11.

12.

987

Fishman P, Falach-Vaknine E, Zigelman R, Bakimer R, Sredni B, Djaldetti M, Shoenfeld Y: Prevention of fetal-loss in experimental anti-phospholipid syndrome by in vivo administration of recombi- nant interleukin-3. J Clin Invest 91 :1834-1837, 1993 Bakimer R, Gilburd B, Zurgil N, Shoenfeld Y: The effect of intravenous gammaglobulin on the induction of experimental antiphospholipid syndrome. Clin Immunol Immunopathol 69:97- 102, 1993 Shoenfeld Y: Idiotypic induction of autoimmunity: do we need an autoantigen? Clin Exp Rheumatol 12 (suppl ll):S37-S40, 1994 Shoenfeld Y: Anti-DNA antibodies: is DNA a self antigen or shelf antigen or are autoimmune rheumatic diseases immunogen driven? Rheumatol Eur 24 (suppl 2):17-20, 199.5 Shoenfeld Y: Idiotypic induction of autoimmunity: a new aspect of the idiotypic network. FASEB J 8:1296-1301, 1994 Damianovich M, Gilburd B, George J, Del Papa N, Afek A, Goldberg I, Kopolovic Y, Roth D, Barkai G, Meroni PL, Shoen- feld Y Pathogenic role of anti-endothelial cell antibodies in vasculitis. J Immunol 156:4946-4951, 1996

Reply To the Editor:

We appreciate the comments of Drs. Beliveau, Da- genais, and MCnard and agree with many of the points that they make, which reiterate those in our previous correspon- dence (Langford CA, Sneller MC: Finding a valid model for human Wegener’s granulomatosis: comment on the article by Tomer et a1 [letter]. Arthritis Rheum 38:1262, 1996). However, we take issue with their comment that PR3 is a protein found only in humans and primates, and not in the mouse. The genetic sequence of mouse PR3 was recently presented at the 7th International Meeting on ANCA and ANCA-Related Disorders, by Dr. Dieter E. Jenne of the Max-Planck-Institute (Martinsried, Germany). The murine complementary DNA sequence has been fully cloned and sequenced in Dr. Jenne’s laboratory and encodes an enzyme with very similar structural properties to those of the human enzyme (Jenne DE: personal communication). Thus, at least some members of the ANCA research community believe that murine PR3 does exist. Until these data are published and available for review by the scientific community, we consider it premature to state that PR3 is an enzyme found only in humans and primates. However, we would concur that unpublished observations by several investigators have failed to demonstrate cross- reactivity between human anti-PR3 antibodies and murine neutrophils, and it was these observations that stimulated our original correspondence.

Carol A. Langford, MD, MHS Michael C. Sneller, MD National Institutes of Allergy and Infectious Diseases National Institutes of Health Bethesda, MD

Cytokine expression in the salivary glands of Sjogren’s syndrome patients in relation to tissue infiltration and lymphoepithelial lesions: comment on the article by Ohyama et a1

To the Editor: We read with interest the article by Ohyama et a1 on

cytokine expression in the salivary glands of patients with