Autoantibodies to Nuclear Lamin C in the Eosinophilia—Myalgia Syndrome Associated with L‐Tryptophan Ingestion

Abstract

Objective. To examine the autoantibodies (antinuclear antibodies [ANA]) present in serum from a patient with eosinophilia-myalgia syndrome (EMS).Methods. Sera obtained during the early phase of EMS and following therapy with prednisone were screened by indirect immunofluorescence on HEp-2 cells, and ANA were characterized by immunoblotting on a purified nuclear lamin fraction.Results. ANA with a ring-like pattern of nuclear staining were identified at high titer by immunofluorescence, and immunoblotting experiments showed them to be directed against lamin C. The antibody titer declined dramatically after discontinuation of L-tryptophan and therapy with prednisone.Conclusion. This is the first characterization of an antigedautoantibody system associated with EMS. The findings indicate that this EMS-associated autoantibody recognizes epitopes localized in the carboxyterminal region of lamin C. The occurrence of antilamin C autoantibodies in one EMS patient expands the spectrum of clinical conditions associated with these antibodies, and provides evidence for an autoimmune response in EMS.The eosinophilia-myalgia syndrome (EMS) associated with ingestion of L-tryptophan-containing products is a newly recognized multisystem disease characterized by peripheral blood eosinophilia and fibrosis of a variety of tissues (1-3). Although the pathogenesis of EMS is not well understood, several features of the syndrome suggest that an immune response may play a role. These features include inflammatory cell infiltrates in various organs (3), activated T lymphocytes in peripheral blood and affected tissues (4), and antinuclear autoantibodies (ANA) in the sera of -50% of EMS patients (5). The antigens recognized by EMS-associated autoantibodies have not yet been characterized. We describe here autoantibodies to lamin, a nuclear envelope component, in the serum of a patient with EMS. We know of no previous reports of such an association. Furthermore, this is the first identification of an antigen recognized by EMS-associated autoantibodies. CASE REPORTThe patient, a 43-year-old woman who had taken L-tryptophan for 2 years, developed swelling of her legs, severe generalized myalgia, and a macular rash on her chest. During the following month, numbness, muscle weakness, and progressive cutaneous induration were noted in all extremities. After discontinuation of L-tryptophan, the rash and myalgias resolved, but the other symptoms became more severe. Physical examination 4 months after the onset of symptoms disclosed induration of the skin of her legs and forearms. She had no facial or digital sclerosis, nailfold capillary abnormalities, or synovitis. Neurologic examina-

Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome.

“…It would be of interest to determine if CFS cases related to xenobiotic agents have similar immune reactivities with NE antigens as the general population of CFS patients. In this regard, Varga et al (35) recently described a patient who developed autoantibodies to lamin C after L-tryptophan ingestion.…”

A heretofore undisclosed crux of Eosinophilia-Myalgia Syndrome: compromised histamine degradation

“…The two unusual features of the allergic secretory response are, fi rstly, that the secretagogue is a specifi c antigen and secondly, that the membrane receptor through which it acts requires the prior attachment of reaginic IgE molecules to become functional" [88]. 40 Some EMS patients also manifest an autoimmune component [308,309], and aberrations in tryptophan metabolism have long been associated with autoimmune diseases [310]. According to several epidemiologists, host susceptibility bias (among other little-known shortcomings) [46,264,303,[311][312][313][314][315][316] undercut the few case-control studies on EMS performed; hence, statistical (epidemiological) underpinnings purportedly supporting a contaminant theory's primacy as well.…”

Immunologic Disturbances in Primary Pulmonary Hypertension

“…Lung involvement with PHT is also a sequella of the L-tryptophaninduced eosinophilia-myalgia syndrome. 34 Patients with the eosinophila-myalgia syndrome have au toantibodies directed against lamin C. 35 5-Hydroxytryptamine, a metabolite of tryptophan, has been implicated in monocrotaline-induced PHT in rats.…”