RESEARCH



Our research is mainly focused on Sjögren's syndrome, a common rheumatic disease, but are also involved in research projects on other rheumatic diseases.



Sjögrens syndrom


Sjögrens syndrom, med en prevalens opp mot 0.5 %, er en kronisk, revmatisk autoimmun sykdom som hovedsakelig rammer kvinner og er karakterisert ved betennelse i eksokrine kjertler. Kardinalsymptomer er tørrhet i øyne og munn som følge av nedsatt tåre- og spyttproduksjon. Rundt 5% av pasientene utvikler lymfom.

Sjögrens syndrom kan opptre alene eller sammen med andre revmatiske sykdommer, som oftest reumatoid artritt eller systemisk lupus erythematosus. Det ser ut til å være en opphopning av autoimmune sykdomstillfeller i familier, og at noen er mer disponert for å utvikle sykdommen enn andre. Man har grunn til å tro at genetiske faktorer kan bidra til predisposisjon for Sjögrens syndrom, i tillegg til miljøfaktorer.

Målet med forskningen er å bidra til å avklare medvirkende faktorer av betydning for patogenesen ved autoimmunitet, spesielt ved Sjögrens syndrom. Dette innebærer blant annet kandidatgenanalyse, assosiasjons- og koblings-studier på henholdsvis enkelt individer, familier og murine modeller med Sjögrens syndrom, samt å utføre ekspresjonsstudier på humant og murint vev.

Forskning på Sjögrens syndrom ledes av professor Roland Jonsson, Broegelmanns forskningslaboratorium, Universitetet i Bergen, og er et samarbeid mellom professor Anne Isine Bolstad (Odontologisk institutt); seniorforsker Karl A. Brokstad (BRL); førsteamanuensis Kathrine Skarstein, (Odontologisk institutt); og førsteamanuensis Johan G. Brun (Revmatologisk avdeling, Haukeland Sykehus).

Viktige nasjonale og internasjonale samarbeidspartnere er: Jacob B. Natvig, Institutt for Immunologi, Rikshospitalet, Oslo Roald Omdahl, Klinisk Immunologi, Sentralsjukehuset i Rogaland, Stavanger Rikard Holmdahl, Medicinsk Inflammationsforskning, Lunds Universitet Marta Alarcon Riquelme, Medicinsk Genetikk och Patologi, Uppsala Universitet Marie Wahren-Herlenius, Karolinska Institutet Simon Bowman, University of Birmingham, UK Tom P. Gordon, University of South Australia Ammon Peck (Michael Humphreys-Beher), Univsersity of Florida John B. Harley, Oklahoma Medical Research Foundation


Publikasjoner:



Bokkapitler og oversiktsartikler

Jonsson R, Haga H-J, Gordon TP: Current concepts on diagnosis, autoantibodies and therapy in Sjögren´s syndrome. (Invited Editorial Review) Scand J Rheumatol 29: 341-348, 2000.

Jonsson R, Haga H-J, Gordon T: Sjögren's syndrome. In: Arthritis and Allied Conditions - A Textbook of Rheumatology, Koopman WJ, ed. 14th Edit. Lippincott Williams & Wilkins, Philadelphia, 2001, pp-1736-1759.

Jonsson R, Skarstein K: Experimental models of Sjögren's syndrome. In: The Molecular Pathology of Autoimmune Diseases, eds. Theofilopoulos, Bona. 2nd Edit. Harwood Acad Publ, Chur, 2001, pp-431-446, in press.

Jonsson R, Brokstad K: Sjögren´s syndrome. In: Samter´s Immunologic Diseases. Austen, Frank, Atkinson, Cantor, eds. 6th Edit. Lippincott Williams & Wilkins, Philadelphia, 2001, pp-in press.

Jonsson R; Sjögren´s syndrome. In: Classics in Rheumatology, Dieppe P, Schumacher R, Wollheim F, eds. Oxford: Isis Medical Media Ltd 2001; in press. Gordon TP, Bolstad AI, Rischmueller M, Jonsson R, Waterman SA: Autoantibodies in primary Sjögren´s syndrome: New insights into mechanisms of autoantibody diversification and disease pathogenesis. Autoimmunity, in press, 2001.

Genetikk og immunologi

Bolstad AI, Haga H-J, Wassmuth R, Jonsson R. Monozygotic twins with primary Sjögren´s syndrome. J Rheumatol 27: 2264-6, 2000.

Jonsson R, Nakken B, Halse A-K, Skarstein K, Brokstad K, Haga H-J. Inheritance and immunology in Sjögrens syndrome (in Norwegian). Tidsskr Nor Lægeforen 120: 811-814, 2000.

Bolstad AI, Wassmuth R, Haga H-J, Jonsson R. HLA markers and clinical characteristics in Caucasians with primary Sjögren´s syndrome. J Rheumatol, in press, 2001.

Nakken B, Jonsson R, Bolstad AI. Polymorphisms of the Ro52 gene associated with anti-Ro52 autoantibodies in primary Sjögren´s syndrome. Arthritis Rheum 44: 638-646, 2001.

Johansson Å, Sundler M, Kjellén P, Johannesson M, Cook A, Lindqvist A-K, Nakken B, Bolstad AI, Jonsson R, Alarcon-Riquelme M, Holmdahl R. Genetic control of collagen induced arthritis in a cross with NOD and C57Bl/10 mice is dependent on gene regions containing complement C5 and FcgrII genes and is not associated with loci controlling diabetes. Eur J Immunol, in press, 2001.

Magnusson V, Lindquist A-KB, Johanneson B, Gröndal G, Kristjánsdóttir H, Steinsson K, Sturfelt G, Truedsson L, Svenungsson E, Lundberg I, Bolstad AI, Haga H-J, Jonsson R, Klareskog L, Granados J, Alcocer-Varela J, Alarcón-Segovia D, Terwillinger JD, Gyllensten UB, Alarcón-Riquelme ME. Fine mapping of the SLEB2 locus involved in susceptibility to systemic lupus erythematosus. Genomics 70:307-314, 2000.

Autoantistoffer

Robinson CP, Brayer J, Yamachika S, Esch TR, Peck AB, Stewart CA, Peen E, Jonsson R, Humphreys-Beher MG. Transfer of human serum IgG to NOD.Ig_null mice reveals a role for autoantibodies in the loss of secretory function of exocrine tissues in Sjögren's syndrome. Proc Natl Acad Sci (USA) 95: 7538-7543, 1998.

Tengnér P, Halse A-K, Haga H-J, Jonsson R, Wahren-Herlenius M. Detection of anti-Ro/SSA and anti-La/SSB autoantibody producing cells in salivary glands from patients with Sjögren's syndrome. Arthritis Rheum 41: 2238-2248, 1998.

Humphreys-Beher MG, Brayer J, Yamachika S, Peck AB, Jonsson R. An alternative perspective to the immune response in autoimmune exocrinopathy: Induction of functional quiescence rather than destructive autoaggression. Scand J Immunol 49: 7-10 1999.

Halse A-K, Harley JB, Kroneld U, Jonsson R. Ro/SS-A reactive B lymphocytes in salivary glands and peripheral blood of patients with Sjögren's syndrome. Clin Exp Immunol 115: 203-207, 1999.

Halse A-K, Wahren-Herlenius M, Jonsson R. Recombinant Ro/SS-A and La/SS-B reactive B lymphocytes in peripheral blood of patients with Sjögren's syndrome. Clin Exp Immunol 115: 208-213, 1999.

Halse A-K, Tengnér P, Wahren-Herlenius M, Haga H-J, Jonsson R. Increased frequency of IL-6 and IL-10 secreting cells in peripheral blood from patients with primary Sjögren's syndrome. Scand J Immunol 49: 533-538, 1999.

Elagib KE, Børretzen M, Jonsson R, Haga H-J, Thoen J, Thompson KM, Natvig JB. Rheumatoid factors in primary Sjögren´s syndrome use diverse VH region genes, the majority of which show no evidence of somatic hypermutation. Clin Exp Immunol 117: 388-394, 1999.

Elagib KE, Tengnér P, Levi M, Jonsson R, Thompson KM, Natvig JB, Wahren-Herlenius M. Immunoglobulin variable genes and epitope recognition of human monoclonal anti-Ro 52-kd from primary Sjögren´s syndrome. Arthritis Rheum 42: 2471-2481, 1999.

Halse A-K, Wahren-Herlenius M, Marthinussen MC, Jonsson R. Isotype distribution of anti-Ro/SS-A and anti-La/SS-B antibodies in plasma and saliva of patients with Sjögren´s syndrome. Scand J Rheumatol 29: 13-19, 2000.

Apoptose

Bolstad AI, Jonsson R: The role of apoptosis in Sjögren's syndrome. Ann Med Interne 149: 25-29, 1998.

Loro JL, Vintermyr OK, Johannessen AC, Liavaag PG, Jonsson R. Suppression of Fas receptor and negative correlation of Fas ligand with apoptosis and differentiation in oral squamous cell carcinoma. J Oral Pathol Med 28:82-87, 1999.

Loro LL, Vintermyr OK, Liavaag PG, Jonsson R, Johannessen AC. Decreased bcl-2/bax expression is associated with increased apoptosis in oral squamous cell carcinoma. Hum Pathol 30: 1097-1105, 1999.

Bolstad AI, Wargelius A, Nakken B, Haga H-J, Jonsson R. Fas and Fas ligand gene polymorphisms in primary Sjögren´s syndrome. J Rheumatol 27: 2397-405, 2000.

Ohlsson M, Skarstein K, Bolstad AI, Johannessen AC, Jonsson R. Fas-induced apoptosis is a rare event in Sjögren´s syndrome. Lab Invest 81: 95-105, 2001.

Klinikk og diagnostikk

Haga H-J, Hultén B, Bolstad AI, Ulvestad E, Jonsson R. Reliability and sensitivity of diagnostic tests for primary Sjögren´s syndrome. J Rheumatol 26: 604-608, 1999.

Haga H-J, Jonsson R. The influence of age on disease manifestations and serological characteristics in primary Sjögren's syndrome. Scand J Rheumatol 28: 227-232, 1999.

Voulgarelis M, Dafni UG, Isenberg DA, Moutsopoulos HM and Members of the European Concerted Action on SS: Jonsson R, Haga H-J, et al. Malignant lymphoma in primary Sjögren´s syndrome - A multicenter, retrospective, clinical study by the European Concerted Action on Sjögren´s syndrome. Arthritis Rheum 42: 1765-1772, 1999.

Bowman SJ, Pillemer S, Jonsson R, Asmussen K, Vitali C et al. Perspectives on outcome measures in primary Sjögren´s syndrome. Rheumatology, in press.

Pasientopplysning

Haga H-J, Jonsson R: Sjögrens syndrom - en orientering for pasienter (In Norwegian). Norsk Revmatikerforbund, pp.1-31, 1998.

Haga H-J, Jonsson R: Sjögrens syndrom - en orientering för patienter (In Swedish). Reumatikerförbundet (Sweden). pp. 1-20, 2000.