Abstract
In rare cases, the monoclonal immunoglobulin that characterizes essential monoclonal gammopathy interacts with a self-antigen with functional consequences and a resulting clinical syndrome. This event is presumably random and results from the clone of B lymphocytes making a monoclonal immunoglobulin that simulates an autoimmune antibody. Thus, by chance, the monoclonal immunoglobulin has sufficient affinity for an epitope on a normal protein that functional consequences ensue. One such rare event is the synthesis and secretion of a monoclonal immunoglobulin that binds to human insulin. Inactivation of insulin by antibody results in (1) an early postprandial hyperglycemia, (2) followed by either or both (i) a reactive overshot in insulin secretion, as a result of hypertrophied or hyperplastic islet beta cells, later falling glucose levels, and (ii) an unpredictable dissociation of insulin from the complex, and, several hours later, (3) a resultant increase in free insulin levels and severe hypoglycemia with clinical consequences, ranging from sweating, dizziness, headache, and tremors to confusion, seizures, and unconsciousness. These attacks are invariably responsive to glucose administration. This very uncommon manifestation of a monoclonal gammopathy can occur in patients with essential monoclonal gammopathy or myeloma. The monoclonal anti-insulin immunoglobulin in monoclonal gammopathy has a low affinity for insulin, but has a high capacity for insulin-binding, resulting in the syndrome of episodic hypoglycemic attacks. This phenomenon of an insulin-binding monoclonal immunoglobulin simulates the acquired insulin autoimmune syndrome, although the latter is mediated by a polyclonal antibody response in the majority of cases studied, and has linkage to HLA class II alleles.
Highlights
Essential monoclonal gammopathy, which is usually an asymptomatic state, may cause an associated disorder because the monoclonal immunoglobulin is of an aberrant physicochemical structure and (1) can form paracrystalline or crystalline deposits in certain tissue, notably the cornea or the kidney, thereby leading to crystalline keratopathy or a renal impairment syndrome; (2) can be deposited in macrophages resulting in crystal-storing histiocytosis, usually involving organs of the mononuclear phagocyte system, and other tissues, including the orbit; or (3) can exhibit exaggerated copper-binding and deposition of copper in the Descemet membrane, a tissue stratum between the stroma and endothelium of the cornea.[1]
We review the rare cases in which the monoclonal immunoglobulin, acting as an insulin-binding autoantibody, simulates the insulin autoimmune syndrome
An insulin-binding monoclonal immunoglobulin, as described in the cases of essential monoclonal gammopathy and myeloma above, can simulate the insulin autoimmune syndrome, which has the following four features: (1) recurrent episodes of symptomatic hypoglycemia, sometimes leading to unconsciousness; (2) a response to glucose administration; (3) very high levels of plasma immunoreactive insulin; and (4) plasma antihuman insulin antibodies in the absence of prior exposure to insulin.[13]
Summary
Essential monoclonal gammopathy (synonymous with monoclonal gammopathy of unknown significance), which is usually an asymptomatic state, may cause an associated disorder because the monoclonal immunoglobulin is of an aberrant physicochemical structure and (1) can form paracrystalline or crystalline deposits in certain tissue, notably the cornea or the kidney, thereby leading to crystalline keratopathy or a renal impairment syndrome; (2) can be deposited in macrophages resulting in crystal-storing histiocytosis, usually involving organs of the mononuclear phagocyte system, and other tissues, including the orbit; or (3) can exhibit exaggerated copper-binding and deposition of copper in the Descemet membrane, a tissue stratum between the stroma and endothelium of the cornea.[1]. In 1989, a second case of essential monoclonal gammopathy in a 64-year-old man was found to be responsible for a hypoglycemic syndrome indistinguishable from the insulin autoimmune syndrome.[5] The patient had episodes of sweating, drowsiness, palpitations, and sometimes grand mal seizures and coma His blood sugar was
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