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  • Review Article

    Mechanisms of Disease: IgG4-Related Disease

    IgG4-related disease is a newly recognized fibroinflammatory condition characterized by tumefactive lesions, a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and, often but not always, elevated serum IgG4 concentrations. The disease was not recognized as…

    • February 9, 2012
    • Stone J.H., Zen Y., Deshpande V.
    • N Engl J Med 2012; 366:539 - 551

      A number of autoimmune diseases that affect diverse organ systems have recently been noted to be related to IgG4 autoantibodies. The authors review the spectrum of IgG4-related disease and the current status of diagnostic and management approaches.

    • Case Records of the Massachusetts General Hospital

      Case 4-2012 — A 37-Year-Old Man with Muscle Pain, Weakness, and Weight Loss

      Presentation of Case. Dr. Ian J. Barbash (Medicine): A 37-year-old man was admitted to this hospital because of muscle pain and weakness. The patient had been well until the evening before admission, when mild diffuse myalgias developed. He awoke in the morning with diffuse muscle cramps and…

      • February 9, 2012
      • Rhee E.P., Scott J.A., Dighe A.S.
      • N Engl J Med 2012; 366:553 - 560
      • CME

      A 37-year-old man was admitted to this hospital because of 12 hours of muscle pain and weakness, resulting in the inability to rise from bed. Brief episodes of similar symptoms had occurred during the past month. He reported blurred vision, gynecomastia, and weight loss.

    • Original Article

      Cold Urticaria, Immunodeficiency, and Autoimmunity Related to PLCG2 Deletions

      The genetic dissection of unique inflammatory phenotypes can identify and elucidate immunologic pathways and mechanisms. Such investigations have ultimately led to findings whose significance extends beyond the monogenic diseases harboring the mutations. Examples include the recognition that FOXP3…

      • January 26, 2012
      • Ombrello M.J., Remmers E.F., Sun G., et al.
      • N Engl J Med 2012; 366:330 - 338

        Analyses of families affected by cold urticaria, immunodeficiency, and autoimmunity implicate mutations that activate phospholipase Cγ2 (PLCγ2), an enzyme pivotal to the translation of binding events at the cell surface to the intracellular milieu, as a cause of the disease.

      • Clinical Therapeutics

        Fingolimod for Multiple Sclerosis

        Foreword. This Journal feature begins with a case vignette that includes a therapeutic recommendation. A discussion of the clinical problem and the mechanism of benefit of this form of therapy follows. Major clinical studies, the clinical use of this therapy, and potential adverse effects are…

        • January 26, 2012
        • Pelletier D. and Hafler D.A.
        • N Engl J Med 2012; 366:339 - 347
        • CME

        A 37-year-old man with multiple sclerosis has recurrent disease activity despite several previous therapies. Treatment with fingolimod is recommended. Fingolimod blocks the egress of lymphocytes from lymph nodes, preventing them from reaching the central nervous system.

      • Correspondence

        Combined C3b and Factor B Autoantibodies and MPGN Type II

        To the Editor: Membranoproliferative glomerulonephritis (MPGN) type II (MPGN II), also called dense-deposit disease, is a rare glomerular disease that often progresses to end-stage renal disease. MPGN II is associated with complement because of systemic C3 activation and deposition of C3 cleavage…

        • December 15, 2011
        • N Engl J Med 2011; 365:2340 - 2342
        • Free Full Text

        This letter describes two unrelated patients with membranoproliferative glomerulonephritis type 2 and autoantibodies to the two individual components of C3 convertase, factor B and C3. These autoantibodies enhance C3 convertase activity, probably leading to nephritis.

      • Review Article

        Mechanisms of Disease: The Pathogenesis of Rheumatoid Arthritis

        Rheumatoid arthritis is a common autoimmune disease that is associated with progressive disability, systemic complications, early death, and socioeconomic costs. The cause of rheumatoid arthritis is unknown, and the prognosis is guarded. However, advances in understanding the pathogenesis of the…

        • December 8, 2011
        • McInnes I.B. and Schett G.
        • N Engl J Med 2011; 365:2205 - 2219

          The increased understanding of the immune mechanisms of rheumatoid arthritis has led to the development of a considerable number of new therapeutic agents that alter the natural history of the disease and reduce mortality.

        • Review Article

          Mechanisms of Disease: Systemic Lupus Erythematosus

          Although the term "lupus erythematosus" was introduced by 19th-century physicians to describe skin lesions, it took almost 100 years to realize that the disease is systemic and spares no organ and that it is caused by an aberrant autoimmune response. The clinical heterogeneity of the disease forced…

          • December 1, 2011
          • Tsokos G.C.
          • N Engl J Med 2011; 365:2110 - 2121

            The author reviews environmental, genetic, epigenetic, and hormonal factors in systemic lupus erythematosus, its diverse organ manifestations, and the myriad immune abnormalities that characterize this autodestructive disease, which mainly affects women of childbearing age.

          • Original Article

            Regulatory T-Cell Responses to Low-Dose Interleukin-2 in HCV-Induced Vasculitis

            Interleukin-2 has been identified for its capacity to stimulate T cells in vitro and has been used to boost effector immune responses in patients with cancers and infectious diseases. It is a registered indication when used as an adjunct for the treatment of renal-cell carcinoma, but there is a…

            • December 1, 2011
            • Saadoun D., Rosenzwajg M., Joly F., et al.
            • N Engl J Med 2011; 365:2067 - 2077

              This phase 1–phase 2a study of the use of low-dose interleukin-2 to treat vasculitis associated with HCV infection suggests the presence of a therapeutic effect that is mediated by an increase in regulatory T cells.

            • Original Article

              Mycophenolate versus Azathioprine as Maintenance Therapy for Lupus Nephritis

              Systemic lupus erythematosus is an autoimmune disorder often characterized by the development of glomerulonephritis. Renal involvement remains the strongest predictor of morbidity and mortality among patients with lupus, and despite improvements in the management of lupus, the incidence of end…

              • November 17, 2011
              • Dooley M.A., Jayne D., Ginzler E.M., et al.
              • N Engl J Med 2011; 365:1886 - 1895

                In this double-blind, randomized trial, mycophenolate mofetil was superior to azathioprine for maintaining a renal response and preventing relapse in patients with lupus nephritis who had had a response to induction therapy.

              • Editorial

                Toward Better Treatment for Lupus Nephritis

                Systemic lupus erythematosus is a prototypical autoimmune disease that can potentially involve every organ. Its clinical spectrum is therefore extremely heterogeneous and varies from relatively mild cases (e.g. involving only the skin or joints) to life-threatening manifestations, with renal…

                • November 17, 2011
                • Houssiau F.A.
                • N Engl J Med 2011; 365:1929 - 1930

                  Systemic lupus erythematosus is a prototypical autoimmune disease that can potentially involve every organ. Its clinical spectrum is therefore extremely heterogeneous and varies from relatively mild cases (e.g., involving only the skin or joints) to life-...

                • Perspective

                  Evidence-Based Medicine in the EMR Era

                  Many physicians take great pride in the practice of evidence-based medicine. Modern medical education emphasizes the value of the randomized, controlled trial, and we learn early on not to rely on anecdotal evidence. But the application of such superior evidence, however admirable the ambition, can…

                  • November 10, 2011
                  • Frankovich J., Longhurst C.A., Sutherland S.M.
                  • N Engl J Med 2011; 365:1758 - 1759

                    Pediatricians facing critical clinical decisions often lack data on which to draw. The authors recently put their institution's electronic medical record to unusual use to inform a decision about anticoagulation in a patient with systemic lupus erythematosus.

                  • Case Records of the Massachusetts General Hospital

                    Case 34-2011 — A 75-Year-Old Man with Memory Loss and Partial Seizures

                    Presentation of Case. A 75-year-old physician was seen in an outpatient office at this hospital because of memory loss and episodes of near-syncope. The patient had been generally well, except for mild and gradual memory loss, until 7 months earlier, when episodes of diffuse tingling and a…

                    • November 10, 2011
                    • Cash S.S., Larvie M., Dalmau J.
                    • N Engl J Med 2011; 365:1825 - 1833

                      A 75-year-old man was seen because of memory loss and episodes of near-syncope, with word-finding difficulty and unilateral twitching. MRI with contrast material revealed hyperintensity and mild expansion of the left hippocampus, without enhancement.

                    • Clinical Problem-Solving

                      A Bird's-Eye View of Fever

                      Foreword. In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information, sharing his or her reasoning with the reader (regular type). The authors' commentary follows. Stage. A 78-year-old man presented to his…

                      • November 3, 2011
                      • Lee A.I., Koo S., Vaidya A., Katz J.T., Loscalzo J.
                      • N Engl J Med 2011; 365:1727 - 1732

                        A 78-year-old man presented with a 4-month history of worsening fatigue, weakness, and anorexia, with an unintentional weight loss of 11.4 kg. He reported fevers, chills, night sweats, dry mouth, nonproductive cough, dyspnea with minimal exertion, nausea, and postural light-headedness.

                      • Correspondence

                        Hemophilia A Induced by Ipilimumab

                        To the Editor: Ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte–associated antigen 4, has been reported to improve overall survival in patients with metastatic melanoma. Major side effects include immune-related adverse events. We report a rare and severe case of ipilimumab…

                        • November 3, 2011
                        • N Engl J Med 2011; 365:1747 - 1748
                        • Free Full Text

                        A case is reported in which ipilimumab therapy for melanoma was followed by the development of an autoantibody to factor VIII.

                      • Review Article

                        Genomic Medicine: Genomics and the Multifactorial Nature of Human Autoimmune Disease

                        The major autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, type 1 diabetes mellitus, psoriasis, and inflammatory bowel disease, share epidemiologic, clinical, and therapeutic features. In each of these diseases, chronic and often intermittent…

                        • October 27, 2011
                        • Cho J.H. and Gregersen P.K.
                        • N Engl J Med 2011; 365:1612 - 1623
                        • Free Full Text

                        This article reviews the many new insights into autoimmune disease brought about through genomic investigations.

                      • Case Records of the Massachusetts General Hospital

                        Case 30-2011 — A 62-Year-Old Woman with Renal Failure

                        Presentation of Case. Dr. Kyle Staller (Medicine): A 62-year-old woman was admitted to this hospital because of renal failure. The patient had an autoimmune overlap syndrome with polymyositis, treated with prednisone and mycophenolate mofetil, but had been in her usual health until 6 weeks before…

                        • September 29, 2011
                        • Cunningham J., Harisinghani M.G., Taheri D.
                        • N Engl J Med 2011; 365:1233 - 1243
                        • CME

                        A 62-year-old woman with autoimmune overlap syndrome and polymyositis presented to this hospital with anemia, thrombocytopenia, and acute renal failure. Four days before admission, she was found on the floor of her home, confused and minimally conversant.

                      • Case Records of the Massachusetts General Hospital

                        Case 28-2011 — A 74-Year-Old Man with Pemphigus Vulgaris and Lung Nodules

                        Presentation of Case. Dr. Omobolaji T. Campbell (Infectious Diseases): A 74-year-old man was seen in the surgery clinic at this hospital for evaluation of lung nodules. A diagnosis of pemphigus vulgaris had been made 5 months earlier after a 2-month history of skin lesions that had progressed from…

                        • September 15, 2011
                        • Mylonakis E., Muse V.V., Mino-Kenudson M.
                        • N Engl J Med 2011; 365:1043 - 1050
                        • CME

                        A 74-year-old man with pemphigus vulgaris was referred to this hospital for evaluation of lung nodules. Imaging of the chest revealed multiple ill-defined nodules, some with marked 18F-fluorodeoxyglucose avidity. A diagnostic procedure was performed.

                      • Clinical Implications of Basic Research

                        Illuminating Immune Privilege — A Role for Regulatory T Cells in Preventing Rejection

                        Bone marrow transplantation has had a substantive therapeutic impact on survival, but its usefulness can be limited by the lack of matched donors, as well as by the risks of graft rejection and graft-versus-host disease (GVHD). Current strategies attempt to address these issues with conditioning…

                        • September 8, 2011
                        • Reya T.
                        • N Engl J Med 2011; 365:956 - 957

                          A recent study suggests that regulatory T cells are relevant in reducing the need for immunosuppressive drugs and in overcoming the limitations of a genetic mismatch between donor and recipient in allogeneic hematopoietic-cell transplantation.

                        • Clinical Implications of Basic Research

                          Systemic Lupus Erythematosus and the Neutrophil

                          Most physicians can identify B lymphocytes and T lymphocytes, and perhaps dendritic cells, as the cells involved in the pathogenesis of systemic lupus erythematosus (SLE). This systemic autoimmune disease is characterized by the loss of tolerance to nuclear antigens, the deposition of immune…

                          • August 25, 2011
                          • Bosch X.
                          • N Engl J Med 2011; 365:758 - 760

                            Recent studies implicate a peculiar form of neutrophil death and its extracellular sequelae in mediating inflammation in patients with systemic lupus erythematosus.

                          • Clinical Therapeutics

                            Thrombopoietin-Receptor Agonists for Primary Immune Thrombocytopenia

                            Foreword. This Journal feature begins with a case vignette that includes a therapeutic recommendation. A discussion of the clinical problem and the mechanism of benefit of this form of therapy follows. Major clinical studies, the clinical use of this therapy, and potential adverse effects are…

                            • August 25, 2011
                            • Imbach P. and Crowther M.
                            • N Engl J Med 2011; 365:734 - 741
                            • CME

                            A young woman with immune thrombocytopenia (ITP) who has been treated with a thrombopoietin-receptor agonist presents for advice regarding long-term treatment. The agents in this therapeutic class, romiplostim and eltrombopag, are effective in increasing platelet counts.

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                          Medical Meetings Conferences and Meetings

                          American Association for the Study of Liver Diseases

                          The following courses will be offered in Atlanta, unless otherwise indicated: "Hepatitis Single Topic Conference: HCV Direct Antiviral Agents (DAA): Concepts, Development and Optimal Use" (March 16 and 17); "The Henry M. and Lillian Stratton Basic Research Single Topic Conference: Mitochondria and Hepatotoxicity" (June 8 and 9); "Clinical Research Single Topic Conference: Acetaminophen Poisoning" (June 9 and 10); and "63rd Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting 2012" (Boston, Nov. 9-13).

                          Contact AASLD, 1001 North Fairfax St., Suite 400, Alexandria, VA 22314; or call (703) 299-9766; or see http://www.aasld.org .

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