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Neuromyelitis optica (NMO) is a severe inflammatory autoimmune CNS disorder triggered by binding of an IgG autoantibody to the aquaporin 4 (AQP4) water channel on astrocytes. Activation of cytolytic complement has been implicated as the major effector of tissue destruction that secondarily involves myelin. We investigated early precytolytic events in the evolving pathophysiology of NMO in mice by continuously infusing IgG (NMO patient serum-derived or AQP4-specific mouse monoclonal), without exogenous complement, into the spinal subarachnoid space. Motor impairment and sublytic NMO-compatible immunopathology were IgG dose dependent, AQP4 dependent, and, unexpectedly, microglia dependent. In vivo spinal cord imaging revealed a striking physical interaction between microglia and astrocytes that required signaling from astrocytes by the C3a fragment of their upregulated complement C3 protein. Astrocytes remained viable but lost AQP4. Previously unappreciated crosstalk between astrocytes and microglia involving early-activated CNS-intrinsic complement components and microglial C3a receptor signaling appears to be a critical driver of the precytolytic phase in the evolving NMO lesion, including initial motor impairment. Our results indicate that microglia merit consideration as a potential target for NMO therapeutic intervention., Introduction Neuromyelitis optica (NMO) is an inflammatory autoimmune disorder of the central nervous system (CNS) with secondary myelin loss. It disproportionately affects women and non-White populations, typically presents as optic [...]

OBJECTIVE: To define the diagnostic characteristics and predictors of treatment response in patients with suspected autoimmune dementia. PATIENTS AND METHODS: Between January 1, 2002, and January 1, 2009, 72 consecutive [...]

OBJECTIVE: To evaluate the prevalence and pathogenetic mechanisms of postural orthostatic tachycardia syndrome (POTS). PATIENTS AND METHODS: We reviewed the medical records of patients with POTS seen at the Mayo [...]

Some types of autoimmune nerve diseases produce antibodies against the ganglionic acetylcholine receptor, according to a study of 157 patients with various types of autoimmune nerve disease. Twenty-five had antibodies against the ganglionic acetylcholine receptor.

Patients with the Lambert-Eaton syndrome may have predominance of antibodies of the P/Q type. P/Q-type antibodies are antagonists of a subtype of calcium channels that are responsible for abnormal cell behavior. Lambert-Eaton syndrome is a paraneoplastic disorder characterized by its own immune response against parts of tumor cells. Paraneoplastic syndromes, often associated with small-cell lung carcinoma, may contain the calcium channel subtypes L, N, and P/Q. Researchers searched for antibodies of these three subtypes in the blood samples of patients with cancer and other diseases. All 32 patients with the Lambert-Eaton syndrome and diagnosed cancer had autoantibodies specific for P/Q-type calcium channels. Also, 30 of 33 patients with the Lambert-Eaton syndrome but without cancer had P/Q-type calcium-channel antibodies. The N subtype appeared to a lesser degree in cancerous conditions.

The presence of a tumor may affect the chemical processes of the body. A 47-year-old woman reported weakness and aching in her arms and legs. A hemangioma, or tumor consisting of blood vessels, was removed from her thigh. Her condition, diagnosed as oncogenic osteomalacia, improved. Oncogenic osteomalacia is a softening of the bones resulting from a tumor or cancer. A medium of sclerosing hemangioma cells extracted from the tumor was found to inhibit phosphate transport in renal epithelial cells without increasing cellular concentrations of cyclic adenosine monophosphate (cAMP). The medium had a low molecular weight and was sensitive to heat.

The presence of more than one autoimmune disease (one in which the body manufactures antibodies against its own proteins) in a patient at the same time is fairly common, exemplified by the frequent coexistence of myasthenia gravis (MG; a relapsing neuromuscular disorder) and adult rheumatoid arthritis. Two case histories are presented of children with juvenile arthritis (JA) and MG, a rare combination since JA is usually present alone. The patients had pauciarticular JA (disease affecting only a few joints). One was diagnosed with JA at the age of six and one half, and developed weakness, slurred speech, and difficulty swallowing at the age of nine. The arthritis was inactive when MG was diagnosed but flared up again several months after the thymus was removed (a treatment for MG in many cases). The second case involved a girl who was 13 when diagnosed with JA. At age 16, she developed muscle weakness and was ultimately diagnosed with MG. Both patients underwent treatment for their conditions. The coexistence of JA and MG in two children seen in the same clinic was surprising, since they are so rarely seen together. Two other cases have appeared in the literature where JA preceded MG by a few years. The family histories of the two patients presented here showed the presence of other possibly autoimmune diseases. A common defect of the immune system is postulated. Children with JA who complain of weakness should be tested for antibodies against the acetylcholine receptor (a sign of MG) and evaluated for abnormalities of muscle function. (Consumer Summary produced by Reliance Medical Information, Inc.)

Drugs that block the FcRn receptor for immunoglobulin G (IgG) may be beneficial in the treatment of autoimmune diseases. Intravenous IgG has often been used to treat autoimmune diseases, although the way it works is not known. Research led to the discovery of the FcRn receptor, which binds IgG. This protects the IgG from being metabolized. If an autoimmune disease is caused by excessive IgG levels, blocking the FcRn receptor would cause more IgG to be metabolized, reducing the excess levels.