Studies on the Pathogenesis of Rheumatoid Joint Inflammation
Authors: JOSEPH LEE HOLLANDER
Journal: Annals of Internal Medicine (1965)

Article1 February 1965Studies on the Pathogenesis of Rheumatoid Joint InflammationI. The "R.A. Cell" and a Working HypothesisJOSEPH LEE HOLLANDER, M.D., F.A.C.P., DANIEL J. MCCARTY JR., M.D., F.A.C.P., GONZALO ASTORGA, M.D., EDUARDO CASTRO-MURILLO, M.D.JOSEPH LEE HOLLANDER, M.D., F.A.C.P., DANIEL J. MCCARTY JR., M.D., F.A.C.P., GONZALO ASTORGA, M.D., EDUARDO CASTRO-MURILLO, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-62-2-271 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe etiology and pathogenesis of rheumatoid arthritis are not known. Many studies have described the clinical and pathological characteristics of the disease process. Numerous additional studies have produced evidence that disorders of immunity are involved, that is, that rheumatoid arthritis and associated diseases may be "immunodyscrasias." Little evidence has been forthcoming to bridge the gap between the clinical features of rheumatoid arthritis and the disordered immunological mechanisms involved.The purpose of this and the next two reports is to describe preliminary findings that may help to clarify the pathogenetic mechanism of rheumatoid arthritis, although the etiology remains unknown. The original...References1. HOLLANDERRAWSONRESTIFOLUSSIER JLAJRAAJ: Studies on the pathogenesis of rheumatoid joint inflammation (abstract). Arthritis Rheum. 7: 314, 1964. Google Scholar2. MCCARTYHOLLANDER DJJL: Identification of urate crystals in gouty synovial fluid. Ann. Intern. Med. 54: 452, 1961. LinkGoogle Scholar3. MCCARTY DJ: Phagocytosis of urate crystals in gouty synovial fluid. Amer. J. Med. Sci. 243: 288, 1962. CrossrefGoogle Scholar4. JACKSON JF: The cytology of the degenerating leukocyte. J. Lab. Clin. Med. 43: 227, 1954. MedlineGoogle Scholar5. IZAKDEVRIES GA: Studies on lipophagocytosis. I. Lipophagocytosis by human white blood cells in vitro and in vivo. J. Lab. Clin. Med. 55: 564, 1960. MedlineGoogle Scholar6. MAJNO G: Mechanisms of abnormal vascular permeability in acute inflammation. In Injury, Inflammation and Immunity, edited by THOMAS, L., UHR, J. W., GRANT, L., Williams and Wilkins Co., Baltimore, 1964. Google Scholar7. FRANKLINEDELMANKUNKEL ECGHG: The rheumatoid factor. In Immunity and Virus Infection, edited by NAJJAR, V. A., John Wiley & Sons, Inc., New York, 1959. Google Scholar8. SINGERPLOTZ JMCM: The latex fixation test in rheumatoid arthritis. Amer. J. Med. 21: 888, 1956. CrossrefMedlineGoogle Scholar9. ASTORGABOLLET GAJ: Diagnostic specificity and possible pathogenetic significance of inclusion-body cells in synovial fluid (abstract). Arthritis Rheum. 7: 288, 1964. Google Scholar10. PARKERSCHMID RLFR: Phagocytosis of particulate complexes of gamma globulin and rheumatoid factor. J. Immun. 88: 519, 1962. MedlineGoogle Scholar11. RAWSONABELSONHOLLANDER AJNMJL: Studies on the pathogenesis of rheumatoid joint inflammation. II. Intracytoplasmic particulate complexes in rheumatoid synovial fluids. Ann. Intern. Med. 62: 281, 1965. LinkGoogle Scholar12. MELLORSHEIMERCORCOSKORNGOLD RCRJL: Cellular origin of rheumatoid factor. J. Exp. Med. 110: 875, 1959. CrossrefMedlineGoogle Scholar13. DEDUVE C: Lysosomes, a new group of cytoplasmic particles, in Subcellular Particles, edited by HAYASHI, T. The Ronald Press Co., New York, 1959. Google Scholar14. ROPESBAUER MWW: Synovial Fluid Changes in Joint Disease, Harvard University Press, Cambridge, 1953. Google Scholar15. SEEGMILLERHOWELLMalawista JERRS: The inflammatory reaction to sodium urate. JAMA 180: 469, 1962. Google Scholar16. MCCARTYKOHNFAIRES DJNNJS: The significance of calcium phosphate crystals in the synovial fluid of arthritic patients: the pseudogout syndrome. Ann. Intern. Med. 56: 711, 1962. LinkGoogle Scholar17. BLANDCLARK JHL: Rheumatoid factor in serum and synovial fluid. Ann. Intern. Med. 58: 829, 1963. LinkGoogle Scholar18. RODNANEISENBEISCREIGHTON GPCHAS: On the occurrence of rheumatoid factor in synovial fluid. Arthritis Rheum. 5: 316, 1962. Google Scholar19. COCHRANEWEIGLEDIXON CGWCFJ: The role of polymorphonuclear leukocytes in the initiation and cessation of the Arthus vasculitis. J. Exp. Med. 110: 481, 1959. CrossrefMedlineGoogle Scholar20. PHELPSMCCARTY PDJ: Unpublished data. Google Scholar21. HIRSCHCOHN JGZA: Degranulation of polymorphonuclear leukocytes following phagocytosis of micro-organisms. J. Exp. Med. 112: 1005, 1960. CrossrefMedlineGoogle Scholar22. JACOXFELDMAN RFA: Variations of beta glucuronidase concentration in abnormal synovial fluid. J. Clin. Invest. 34: 263, 1955. CrossrefMedlineGoogle Scholar23. SMITHHAMERMAN CD: Acid phosphatase in human synovial fluid. Arthritis Rheum. 5: 411, 1962. CrossrefGoogle Scholar24. ZVAIFLERPEKIN NJTJ: Complement components in synovial fluids (abstract). Arthritis Rheum. 6: 308, 1963. Google Scholar25. FOSTIROPOULOSAUSTENBLOCH GKFKJ: Total hemolytic complement and second component of complement activity in serum and synovial fluid of patients with rheumatic diseases (abstract). Arthritis Rheum. 7: 308, 1964. Google Scholar26. RESTIFOLUSSIERRAWSONROCKEYHOLLANDER RAAJAJJHJL: Studies on the pathogenesis of rheumatoid joint inflammation. III. The experimental production of joint inflammation by intra-articular injection of purified 7S gamma globulin in rheumatoid arthritis. Ann. Intern. Med. 62: 285, 1965. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Philadelphia, PennsylvaniaFrom the Arthritis Section, Department of Medicine, Hospital of the University of Pennsylvania, and the Section of Rheumatology, Department of Medicine, Hahnemann Medical College and Hospital, Philadelphia, Pa.Parts of this paper were read in condensed versions before the Eighth Japan Rheumatism Congress in Okayama, Japan, May 20, 1964, and before the Annual Meeting of the American Rheumatism Association in San Francisco, Calif., June 18, 1964 (1). Versions of this paper were also presented before the Australian Rheumatism Congress in Sydney, Australia, September 11, 1963, the Third Pan-American Congress of Rheumatology in Santiago, Chile, October 16, 1963, and the Regional Meeting of the American College of Physicians in Philadelphia, Pa., November 8, 1963.Requests for reprints should be addressed to Joseph L. Hollander, M.D., Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, Pa. 19104. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByCitodiagnóstico del líquido sinovialTendons, Joints, and BoneTendons, Joints, and BoneGelenkpunktion und -injektion – Die GeschichtePleural, Peritoneal, and Pericardial EffusionsHypothesis: The Humoral Immune Response to Oral Bacteria Provides a Stimulus for the Development of Rheumatoid ArthritisPathogenesis of Rheumatoid ArthritisReaktionsformen des organisierten BindegewebesT cells as secondary players in rheumatoid arthritisSimultaneous generation of nitric oxide and superoxide by inflammatory cells in ratsHistopathology of the Rheumatoid JointPathogenetic concepts and origins of rheumatoid factor in rheumatoid arthritisIn vivo leukocyte migration in arthritisThe Total Cell Count and the 'Wet Prep' Examination and Interpretation 1. CellsTurpentine- and fibrin-induced pleuritis in nude miceRheumatoid arthritis cells and biochemical changes in turpentine-induced pleuritis in rabbitsComparison of serial synovial fluid cytology in rheumatoid arthritis: delineation of subgroups with prognostic implications.LysosomesMuramidase (Lysozyme) in Joint Fluid and Serum of Rheumatic PatientsThe pharmacological basis of antirheumatic drug therapyAcute Synovitis Induced by Preformed Immune ComplexesPulmonary manifestations of the rheumatic diseasesLactoferrin in Sjögren's SyndromePleuropulmonary manifestations of rheumatoid arthritisPunktionsdiagnostik und GelenkzytologieImmunocytological studies of Epstein-Barr viral antigen and antibody in rheumatoid synovial fluidsNeutrophil migration in response to chemotactic factorsJoint fluid leukocytosis of patient with rheumatoid arthritis computer analysis of possible explanative factorsImmunoelectronmicroscopic Characterization of Intracellular Inclusions in Synovial Fluid Cells of Patients with Rheumatoid ArthritisThe Role of the Ma-Sensitive Leukocyte Chemotaxis in Rheumatoid ArthritisPathogenesis of rheumatoid arthritis: A vascular hypothesisExamination of Synovial FluidThe Cytology of Joint Exudates in Rheumatoid Arthritis: Morphology and Preparation TechniquesCharacterization of the immunocompetent cells of rheumatoid synovium from tissue sections and eluatesPolymorphonuclear Leukocytes (PMN)—Origins, Functions and Roles in the Rheumatic Diseases?2-Macroglobulin as an inclusion in synovial fluid monocytesChronic arthritis of rabbits induced by mycoplasmas II.antibody response and the deposition of immune complexesGranulocyte-Specific Antinuclear Antibodies.Synovial FluidA tissue culture model of cartilage breakdown in rheumatoid arthritisExtraarticular manifestations of rheumatoid arthritisArthritis—Rheumatoid-LikeRheumatoid Arthritis: A Dissertation on its Pathogenesis and Future Directions for Research*Growth and Development of Rheumatology in the United States—A Bicentennial ReportLactoferrin and Lysozyme in Arthritic ExudatesRheumatoid factor-immunoglobulin G complex precipitation and neutrophil stimulation: an in vitro model for rheumatoid inflammationStudies on vasculitis. VI. Antiglobulins or rheumatoid-like factors in cutaneous vasculitis lesions detected by an improved immunofluorescence procedureLymphocyte populations in rheumatoid arthritisJuvenile Rheumatoid Arthritis: A general review and report of 100 patients observed for 15 yearsFINE STRUCTURE OF GRANULOCYTES WITH CYTOPLASMIC INCLUSIONS IN PLEURAL EFFUSIONS FROM PATIENTS WITH RHEUMATOID PLEURITIS, TUBERCULOUS PLEURITIS AND PLEURAL CARCINOMATOSISPARTICIPATION OF GRANULOCYTE-SPECIFIC ANTINUCLEAR FACTORS IN RHEUMATOID JOINT FLUID CRYOPRECIPITATESSYNOVIAL MEMBRANE AND FLUID MORPHOLOGIC ALTERATIONS IN EARLY RHEUMATOID ARTHRITIS: MTCROVASCULAR INJURY AND VIRUS-LIKE PARTICLESTHE ROLE OF THE LYMPHOCYTE AND ITS PRODUCTS IN THE PROPAGATION OF JOINT DISEASEImmunoglobulin phagocytosis by granulocytes from sera and synovial fluids in various rheumatoid and nonrheumatoid diseases.Effects of anti-inflammatory and other compounds on the release of lysosomal enzymes from macrophagesANTIGLOBULIN PRODUCTION TO ALTERED IgG IN RHEUMATOID ARTHRITISRheumatoid ArthritisLiteraturThe Intracellular Neutral SH-Dependent Protease Associated with Inflammatory ReactionsExperimental immune synovitis in the rabbit. Relative roles of cell mediated and humoral immunityThe effect of synovial hyaluronate on the ingestion of monosodium urate crystals by leukocytesCellular immunological aspects of rheumatoid arthritisRheumatoid synovitis. An extravascular immune complex diseaseClinical Utility of Immunosuppressive AgentsDie chronische PolyarthritisDie rheumatoide ArthritisRheumatoid Arthritis, 1970-1972JOHN S. JOHNSON, M.D., JOHN H. VAUGHAN, M.D., F.A.C.P., P. KAHLER HENCH, M.D., STEPHEN E. BLOMGREN, M.D., F.A.C.P.Correlation of Histochemical, Histologic and Biochemical Evaluations of Human Synovium with Clinical ActivityIntra-articular 5-fluorouracil (5-FU) in antigen-induced arthritis: Effect of timing on responseThe Immunopathology of Joint Inflammation in Rheumatoid ArthritisEffect of Gold Salts and Antimalarials on the Rheumatoid Factor in Rheumatoid ArthritisChronic synovitis in rheumatoid arthritisCanine rheumatoid arthritis-a review and a case reportEtiology and pathogenesis of rheumatoid arthritis and related multisystem diseasesAppraisal of Rheumatoid Arthritis as an Immune Complex DiseasePLEURAL EFFUSION IN RHEUMATOID ARTHRITISTHE PRIMARY CAUSE OF RHEUMATOID ARTHRITIS IS AN INFECTION-THE INFECTIOUS AGENT EXISTS IN MILKThe Regenerability of the Synovial Membrane after Subtotal Synovectomy in Experimental Allergic ArthritisRHEUMATIC DISEASES OF THE AGED: DIAGNOSIS AND MANAGEMENT*The Complement System in Rheumatoid Synovitis. II. Intracytoplasmic Inclusions of Immunoglobulins and ComplementImmunological Phenomena in Rheumatoid ArthritisPresent Status of the Rheumatoid FactorProphylactic AntibioticsCytotoxic Drugs in Rheumatoid ArthritisMuramidase (Lysozyme) in Joint Fluid and Serum of Rheumatic PatientsFormation of leukocyte inclusions in normal polymorphonuclear cells incubated with synovial fluidStudies of isolated synovial lining cells of rheumatoid and nonrheumatoid synovial membranesSynovectomy in rheumatoid arthritisFurther speculation on the pathogenesis of joint inflammation in rheumatoid arthritisCardiac tamponade in rheumatoid arthritis. a case report and review of the literatureLeucineaminopeptidase in rheumatoid arthritis. Localization in subchondral bone and in synovial fluid cells.Mediation of Inflammation by the Polymorphonuclear Leukocyte as a Sequela of Immune ReactionsPlasma Kinin Formation in Rheumatoid ArthritisPlasma Kininogenases and Their ActivatorsNeunte wissenschaftliche SitzungMakrophagen: Herkunft, Entwicklung und FunktionAgammaglobulinemia with polyarthritis and subcutaneous nodulesContent of Fibroeartilagenolytic Enzymes and Viscosity of Homogenates of Joint Menisci in Rheumatoid ArthritisImmunological studies of an experimental chronic arthritis resembling rheumatoid arthritisChronic arthritis produced by streptococcal L-formsRELATION OF RHEUMATOID FACTOR TO INTRACELLULAR INCLUSIONS*The removal of aggregated and nonaggregated autologous gamma globulin from rheumatoid jointsRHEUMATOID ARTHRITIS CELLSGILBERT B. BLUHM, M.D.The adverse effect of intravenous iron-dextran in rheumatoid arthritisTHE DIAGNOSTIC IMPORTANCE OF SYNOVIAL FLUID ANALYSISSerum levels of IgG, IgM, and IgA in rheumatoid arthritis.Early Synovectomy in the Treatment of Rheumatoid ArthritisDemonstration of rheumatoid factor in tissue by mixed agglutination with tissue sectionsViews on the Pathogenesis of Rheumatoid ArthritisMechanisms of Inflammation in Rheumatoid ArthritisRole of Lysosomes in the Pathogenesis of Rheumatoid ArthritisCytotoxic Therapy in Rheumatoid ArthritisA New Type of Inclusion Bodies in LymphocytesRelation of intracytoplasmic inclusions in joint fluid leukocytes to anti-γG globulinsLong-term cyclophosphamide therapy in rheumatoid arthritisSome biological and biochemical consequences of inflammation in connective tissueImmunologic Tissue Injury Mediated by Neutrophilic LeukocytesHaemolytic complement level and ragocyte (R A cell) concentration in synovial fluid.Juvenile Rheumatoid ArthritisRheumatoid PericarditisInduction of proliferative synovitis in rabbits by intra-articular injection of immune complexesRecent Advances in the Rheumatic DiseasesEPHRAIM P. ENGLEMAN, M.D., F.A.C.P., MARTIN A. SHEARN, M.D., F.A.C.P.Arthritis—An Example of Inflammation Based on ParticlesAutosensitivity DiseasesThe Clinical Significance of Deoxyribonucleic Acid Particles in Synovial FluidTHOMAS J. PEKIN JR., M.D., THEODORE I. MALININ, M.D., NATHAN J. ZVAIFLER, M.D.Lysosomes and joint diseaseRheumatoid Arthritis and Its Systemic ManifestationsCARL M. PEARSON, M.D., F.A.C.P., EUGENE BARNETT, M.D., RICHARD KROENING, M.D., LEONARD MARMOR, M.D., JOHN F. MURRAY, M.D., JAMES B. PETER, M.D., PH.D., ALLEN SALICK, M.D.Further studies on the pathogenesis of rheumatoid joint inflammationExamination of Synovial Fluid as a Diagnostic Aid in ArthritisA hypothetical common mechanism in systemic lupus erythematosus and rheumatoid arthritisPleural and Pericardial Effusions in Rheumatoid DiseaseHERBERT W. BERGER, M.D., STANLEY G. SECKLER, M.D.LEUCOCYTES IN RHEUMATOID ARTHRITIS7S AND 19S DERMATOTOXIC GLOBULINSA study of distal interphalangeal joint tenderness in rheumatoid arthritisThe phagosomes in rheumatoid synovial fluid leukocytes: A light, a light, fluorescence, and electron microscope studyNonsteroid Antiinflammatory AgentsPolyarthritis psoriaticaNew thoughts on the pathogenesis of rheumatoid arthritisThe effect of penicillamine on the laboratory parameters in rheumatoid arthritisLysosomesCellular reaction to complexes formed between rheumatoid factor and aggregated human gamma globulin.Studies on the Pathogenesis of Rheumatoid Joint Inflammation III. The Experimental Production of Arthritis by the Intra-articular Injection of Purified 7S Gamma GlobulinRONALD A. RESTIFO, M.D., ANDRE J. LUSSIER, M.D., ARNOLD J. RAWSON, M.D., JOHN H. ROCKEY, M.D., JOSEPH LEE HOLLANDER, M.D., F.A.C.P. 1 February 1965Volume 62, Issue 2Page: 271-280KeywordsArthritisEtiologyHospital medicineInflammationPathogenesisPathogensPhagocytosisRheumatoid arthritisRheumatologySynovial fluid Issue Published: 1 February 1965 PDF DownloadLoading ...