Humoral and cellular immune responses to myelin protein peptides in chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVES: Evidence that chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease was sought, by studying cellular and humoral immune responses to peripheral nerve myelin proteins. METHODS: 40 CIDP, 36 healthy control subjects (HC) and subjects with non-immune mediated neuropathies (other neuropathies, ON) for antibodies were studied by ELISA and cellular responses by cytokine ELISPOT (INF gamma, IL10) and ELISA (IL17) to synthetic peptides representing P0, P2 and PMP22. RESULTS: Antibodies to P0, P2 or PMP22 peptides were detected in only a minority of CIDP, both not treated (nT-CIDP) and treated (T-CIDP). IgG antibodies to P2(80-105) were significantly more frequent in CIDP than in HC (4/30 vs 0/32; p<0.05) but the difference from ON (1/25) was not significant. In ELISPOT assays, IFN gamma was detected at a low frequency in CIDP and did not differ from HC or ON. In contrast, IL10 responses against P2(1-85) were more frequent in nT and T-CIDP (7/24 and 3/16) than HC (0/36; p<0.001 and p<0.05, respectively). The production of IL17 in cell-culture supernatants was not increased. CONCLUSIONS: Antibodies to non-conformational antigenic epitopes of myelin proteins rarely occur in CIDP. None of the myelin protein peptides elicited IFN gamma responses, but P2 elicited IL10 responses significantly more often in CIDP patients than in controls. This reactivity may be part of an antigen-specific Th2 type pathogenetic or regulatory mechanism or represent a transitory epiphenomenon due to nerve damage. In our study, P2 was the protein antigen most likely to be involved in the aberrant immune responses in CIDP.

Immune responses to myelin proteins in Guillain-Barré syndrome.

BACKGROUND: Potential target autoantigens in the demyelinating form of Guillain-Barré syndrome (GBS) include the myelin proteins PMP22, P0 and P2. METHODS: We investigated immunoreactivity to P0, P2 and PMP22 proteins in 37 patients with GBS and 32 healthy controls. RESULTS: Antibodies to PMP22 or P0 peptides were detected at presentation in only 5 out of 37 patients. In ELISPOT assays, blood mononuclear cells from 15 out of 24 patients with GBS, but none of the control subjects, produced interleukin-10 (IL-10) in response to peptides from proteins P0, P2 or PMP22 (p = 0.0003). The cells from only two patients produced interferon-gamma (IFN gamma). The cells from 11 patients with GBS had increased IL-10 responses to peptides representing sequences from the extracellular domains of PMP22 before intravenous immunoglobulin (IVIg) treatment (p = 0.006). The cells from 11 patients with GBS, including 7 who responded to the extracellular domains of PMP22, had increased IL-10 responses to the intracellular domain of P0 before (p = 0.005) and those from 9 patients after they had been treated with IVIg (p = 0.01). CONCLUSIONS: Antibodies to P0 and PMP22 protein peptides do occur in GBS but are uncommon. Circulating mononuclear cell IFN gamma responses to P0, P2 and PMP22 myelin protein peptides are rare, but IL-10 responses occur significantly more often than in normal subjects. They might be part of a harmful pathogenetic process or represent a regulatory response.

Chronic inflammatory demyelinating polyradiculoneuropathy: a role for haematopoietic stem cell transplantation?

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a clinical syndrome of a chronic progressive or relapsing and remitting, symmetrical, sensory and motor radiculoneuropathy. The immune reaction in CIDP is characterised by selective inflammation of peripheral nerves and is probably due to the interaction of cellular and humoral responses. Only three treatments for CIDP have demonstrated benefit in randomised studies, corticosteroids, plasma exchange and intravenous immunoglobulin. 25% of patients fail to respond or do not respond adequately to these treatments. Experimental data in animal models have shown that several autoimmune disorders, either congenital or acquired, can be transferred and/or treated by the transplantation of bone marrow stem cells. Haematopoietic stem cell transplantation (HSCT) has been performed with varying success in over 700 patients with autoimmune disorders throughout Europe. The experience in CIDP is very limited. This article will review current understanding of CIDP and experience of the use of HSCT in refractory CIDP.

Peripheral neuropathy in hepatitis C virus infection with and without cryoglobulinaemia.

OBJECTIVES: Hepatitis C virus (HCV) infection is often associated with cryoglobulinaemia (CG). Peripheral neuropathy (PN) is a comparatively common complication of CG associated with HCV infection and it is thought to be attributable to nerve ischaemia. Only few HCV CG patients with PN have been reported. The recent finding of HCV RNA in nerve biopsy specimens has suggested a possible direct role of HCV in the pathogenesis of PN. The authors studied 51 HCV patients to determine the prevalence of CG and to clarify the possible mechanism by which HCV determines the PN. METHODS: All the patients were studied clinically, by laboratory tests and electrophysiologically. Twenty eight patients underwent sural nerve biopsy where both morphological and morphometric evaluation of the biopsy specimen was performed, as well as statistical analysis. RESULTS: CG was found in 40 of 51 cases (78%). Polyneuropathy was significantly prevalent in CG+ patients compared with CG- (18 of 40 compared with 1 of 11 patients; p=0.01). HCV CG- patients more frequently developed well defined mononeuropathy or multiple neuropathy when compared with HCV CG+ (10 of 11 compared with 22 of 40; p<0.03). HCV CG+ patients showed significantly higher proportion of rheumatoid factor positivity (p<0.001) and low C4 levels (p=0.001). Nerve biopsy was performed in 25 of 40 HCV CG+ patients and in 3 of 11 HCV CG- patients: epineurial vasculitis was present in 8 of 25 HCV CG+ (32%) and in 2 of 3 HCV CG-. Differential fascicular loss of axons was found in 10 of 25 CG+ (40%) and 1 of 3 CG-, signs of both demyelination and axonal degeneration were present in 7 of 25 CG+ (28%). No significant difference was found in neuropathological features, while histometrical analysis disclosed more severe involvement in CG+ patients. CONCLUSIONS: These findings suggest that the presence of CG is a negative predictive factor for the associated PN. Morphological findings in the sural nerve from HCV CG- and CG+ are consistent with an ischaemic mechanism of nerve damage and are against a direct role of the virus in causing the associated PN.