Brain tissue immunoglobulins in adrenoleukodystrophy: A comparison with multiple sclerosis and systemic lupus erythematosus

Abstract

Immunoglobulin (Ig) concentrations were investigated in white matter samples of two adrenoleukodystrophy (ALD), three multiple sclerosis (MS), two systemic lupus erythematosus (SLE), one rheumatoid arthritis, and three control brains obtained at autopsy. "Free" Igs were extracted at pH 7.4; subsequently, bound Igs were extracted at pH 2.5 and 10.8, respectively. Igs were quantified by radial immunodiffusion. In ALD material there was an increase of free IgG and IgA, in one sample also of IgM, as compared to controls. No significant amounts of Igs were detected in the pH 2.5 and 10.8 extracts of ALD brain. Similarly to ALD, an increase of free IgG and IgA was a characteristic finding in MS brain; in contrast to ALD and control material, significant amounts of bound Igs (IgG) extractable at acid or alkaline pH, respectively, were present in MS tissue. In both SLE brains increase of free IgM was conspicuous. Preliminary studies on binding of Igs extracted at pH 7.4 from brain to frozen sections of normal human and bovine brain tissue revealed different binding properties of Igs from ALD, MS, SLE, and control brains. Immunochemical findings in ALD indicating pathologic accumulation of Igs in brain tissue were paralleled by immunocytochemical observations demonstrating accumulation of lymphoid cells staining for IgG, IgA, and IgM, respectively, mainly in areas of recent demyelination. Participation of Igs in the pathogenesis of ALD lesions may be considered but needs further confirmation.

Diagnosis and Pathogenesis of Late-Onset Genetic Metabolic Encephaloneuromyopathies

“…The histological similarities between ALD and MS lesions are well known: the inflammatory lesions of the white matter in ALD resemble those of MS, suggesting that immune mechanisms are involved in the pathogenesis of the degeneration of myelin. The pres ence of oligoclonal bands in the spinal fluid of ALD patients and the identification of immune processes [20,21] along with high tissue concentrations of IgG and IgA found by Berheimer et al [61] and the results of im munohistochemical analysis of cerebral macrophages [62] reinforce these hypotheses. It is likely that a change in lipid metabolism renders the myelin particularly vul nerable, predisposing it to MS. Susceptibility to MS is genetically heterogeneous, in other words not all patients have the same genetic susceptibility.…”

T-cell receptor Vβ gene usage in CSF lymphocytes in X-linked adrenoleukodystrophy

“…In the cerebral form of ALD, a striking inflammatory cell response occurs within the demyelinated areas, in the edge of active demyelinating lesions (Schaumburg et al, 1975). Both immunoglobulin and inflammatory cell-mediated lesions have been further suggested (Bernheimer et al, 1983;Griffin et al, 1985;Boutin et al, 1989;Powers et al, 1992). This distribution of cells is similar to that found in the central nervous system (CNS) during a cellular immune response.…”

Effects of subperineurial injections of very-long-chain and medium-chain fatty acids into rat sciatic nerve

“…If VLCFA excess contributes significantly to the pathogenesis of ALD, then implementation and further refinement of this dietary approach would be warranted. Apart from a direct toxic effect of VLCFA, there is also evidence that immunological reactions have a pathogenetic role (Bernheimer et al, 1983;Griffin et al, 1985), possibly secondary to the primary defect in the VLCFA metabolism.…”