Lars Klareskog

Autoimmunity to Collagen II and Myelin Basic Protein: Comparative Studies in Humans and Rodents

The evolution of systems for self-nonself discrimination in long-lived animals such as mammals is bound to face two major problems: (i) to avoid reacting with self in a destructive manner, and (ii) to react with a sufficient number of molecules within a rapidly changing microbial world. Since the fulfilment of these tasks is potentially contradictory, it is not surprising to find that thymic elimination of autoreactive T lymphocytes is not complete and that several mechanisms may operate peripherally to control potentially harmful autoimmunity. The way we have chosen to study and describe problems encountered in selfnonself discrimination in the periphery is infiuenced by the following preconceptions: (i) Those autoimmune reactions that can be of evolutionary significance as unwanted are mainly those that are associated with autoimmune diseases that significantly affect survival or reproduction, (ii) Whether autoimmune reactions that lead to autoimmune diseases after deliberate immunization of experimental animals is a significant problem for the species can best be determined from studies of similar reactions occurring in diseases that emerge also without deliberate immunizations, (iii) Mechanisms exist for compartmentalization of immune reactions so that, hypothetically, immune reactions that are harmful at one site may at another site be non-harmful or even essential for the antimicrobial defence; evidence for the existence of such compartmentalization derives both from the long known existence of a specialized mucosa-bound immune system, and from the more recent demonstrations of different address-

Major histocompatibility complex class II expression and parathyroid autoantibodies in primary hyperparathyroidism

BACKGROUNDnAutoimmune diseases are characterized by induced parenchymal expression of major histocompatibility complex (MHC) class II antigens and circulating autoantibodies directed toward surface structures on the target cells. MHC class II expressions can be modified by viral infections of potential pathogenic importance in autoimmune reactions. Primary hyperparathyroidism exhibits incompletely clarified cause.nnnMETHODSnWith cryosections, human parathyroid glands were stained with monoclonal antibodies to MHC class II antigens according to a peroxidase-antiperoxidase technique. Human parathyroid adenoma tissue transplanted to nude mice and rat parathyroid glands was tested with serum from patients with hyperparathyroidism and control subjects.nnnRESULTSnInduced MHC class II expression was demonstrated on parathyroid parenchymal cells in 13 of 54 adenomatous and eight of 23 hyperplastic glands of patients with primary hyperparathyroidism. This reactivity was absent in 12 normal glands, nine normal-sized glands associated with the adenomas, and 17 enlarged glands of patients with hyperparathyroidism caused by uremia. Staining of parathyroid tissue was found with serum from 27 of 38 patients with primary hyperparathyroidism, whereas this reactivity was absent on rat thyroid and pancreatic tissue, as well as with control sera.nnnCONCLUSIONnThe concurrent induction of MHC class II antigen expression and c circulating antiparathyroid autoantibodies in 16 or 38 patients with primary hyperparathyroidism suggests hitherto unrecognized immunologic involvement in this disease.

Mechanisms Involved in Immunomodulatory Treatment of Rheumatoid Arthritis

Many inflammatory rheumatic diseases, including rheumatoid arthritis, appear to depend on a dysregulation of the immune system, that is, interference with pathogenetically important immune reactions can be expected to have beneficial or even direct curative effects on the respective diseases. Ideally, an adequate therapy would thus require knowledge of which immune reactions are critical for disease development and access to means whereby these but no other reactions could be down-regulated. Even if we are far from this situation both as to pathogenetic knowledge and access of practically working specific immunomodulatory treatment, our emerging knowledge on the immunopathogenesis of rheumatic joint diseases may be used both to reconsider the mode of action of currently used drugs and to critically approach some of the more experimental treatments that have recently been introduced.