Objective. To test for genetic differences in susceptibility to homologous (rat) type I1 collagen-induced arthritis (RII-CIA).Methods. Nine inbred and RT1-congenic rat strains were immunized with native rat type I1 collagen and evaluated for arthritis and IgG anti-RII serum antibody titers.Results. Only RTla"' strains developed a high incidence of severe RII-CIA and high titers of IgG anti-RII serum antibody. Rats having RII-CIAresistant haplotypes, RTI".".' (which are known to develop CIA after immunization with heterologous type I1 collagen), were shown to also be susceptible to passive transfer of CIA with immune serum concentrates. Clinical expression of RII-CIA was down-regulated by non-RT1 genes of BN origin. No strong gender differences in anti-RII autoimmune responses were observed.Conclusion. Arthritogenic, autoimmune reactivity to homologous RII is under strict genetic control but occurs readily in RT1"" rats. Collagen-induced arthritis (CIA) is an experimentally induced model of chronic arthritis that hasFrom The Research Service, Salt Lake City Veteran Affairs Medical Center, and the Division of Rheumatology, University of Utah Medical School, Salt Lake City, Utah.Supported been studied in rats, mice, and primates. Joint inflammation in CIA is due to the generation of collagenreactive T cells and complement-binding, IgG anticollagen antibodies that cross-react with autologous type I1 collagen in joint cartilage (1,2). Several gene products influence the susceptibility of an individual rat to CIA (3-5). Of primary importance are the class I1 molecules that are encoded within the major histocompatibility complex (RTl), and that bind collagen peptides for presentation to T cells by antigen processing cells (5). Equally important are the non-major histocompatibility complex-encoded (non-MHC-encoded), T cell antigen receptor (TCR) molecules, which dictate the strength of interaction between specific T cells and each of the multiple immunogenic peptide fragments of type 11 collagen (6).CIA is commonly induced by immunization with heterologous, native type I1 collagen extracted from the articular cartilage of diverse species including bovine, chick, deer, porcine, and human. The minor, species-specific differences in amino acid sequence that exist among these very conserved molecules are readily detected by the rat immune system and cause an RTl-restricted variability in strain susceptibility to CIA induction by type I1 collagens of different origins (7,8).In this study we analyzed the response of several inbred and RTI-congenic rat strains to immunization with homologous rat type I1 collagen (RII). Of those tested, only one MHC haplotype, RTI"", was associated with a high degree of susceptibility to RII-CIA, although the other haplotypes that were tested are known to promote the induction of CIA by immunization with heterologous type I1 collagens. The results show that MHC-encoded genes determine the

The liver histology of 52 patients treated with intermittent low dose pulse methotrexate for rheumatoid arthritis was evaluated using a modification of the Roenigk grading system. Patients studied had had an average of 3-2 years of treatment or had received 1*7 g methotrexate. No patient had cirrhosis; 15 (29%) patients had evidence of mild fibrosis. Histological abnormalities were not predicted by liver function test changes, with the exception that hypoalbuminaemia occurred in 60-/o of those with grade IV (modified criteria) fndings. The need for liver biopsy in patients with rheumatoid arthritis treated with methotrexate before two years or 1500 mg of treatment has not been established. Whether serial liver biopsies will be needed beyond this time has yet to be determined.

The clinical utility of standard liver function tests for monitoring low dose pulse methotrexate therapy is reviewed in 163 rheumatoid arthritis patients over an eight-year period. Abnormalities of hepatic enzymes were seen in 58% of patients but led to cessation of therapy in only 5%. Moderate alcohol intake did not affect the frequency of liver test abnormalities. Abnormalities were seen more frequently in patients with longer duration of methotrexate therapy and in those with higher total dose. There was no correlation between liver test abnormalities and day of serum sampling relative to day of methotrexate dosing, nor was a correlation seen between liver test abnormalities and total weekly dose of methotrexate. Methotrexate has been demonstrated to be an effective drug in the treatment of rheumatoid arthritis. The clinical utility of standard liver tests to predict the potential for hepatotoxicity is questionable.

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Amyloid arthropathy is said to be distinguished roentgenographically from rheumatoid arthritis by the absence of joint space narrowing and the absence of articular erosions. We present a patient with multiple myeloma with swelling, stiffness and firm synovial thickening of the wrists, metacarpophalangeal joints and proximal interphalangeal joints whose hand radiographs showed articular erosions of the carpal joints and ulnar styloid and joint space narrowing of the proximal interphalangeal joints and metacarpophalangeal joints. Synovial biopsy of the left wrist showed amyloid deposits with no inflammation. Previous reports of X-ray changes in amyloid arthropathy note preservation of joint spaces or widening. Erosions when noted are of non-articular bone rather than of the articular surface. This is the first case report of erosive articular disease in amyloid arthropathy.