James B. Peter

Serum and CSF levels of IL‐2, sIL‐2R, TNF‐α, and IL‐1β in chronic progressive multiple sclerosis Expected lack of clinical utility

We measured interleukin-2 (IL-2), soluble IL-2 receptor (sIL-2R), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) by ELISA in paired sera and CSF from 50 chronic progressive multiple sclerosis (CPMS) patients during worsening disability, 19 patients with other neurologic diseases (OND), and in sera from 40 healthy volunteers. In the CPMS patients, 28% (14/50), 10% (5/50), 16% (8/50), and 6% (3/50) had elevated serum levels of IL-2, sIL-2R, TNF-α and IL-1β, respectively, compared with healthy controls. The only analyte we detected in the CSF was IL-2 in 1 CPMS patient (1/50, 2%). We also saw elevated serum sIL-2R in 16% (3/19) of OND patients. We found no significant difference in mean levels of serum sIL-2R between the 3 groups. Our study, the largest to date of CPMS patients, shows that serum and CSF levels of IL-2, sIL-2R, TNF-α, or IL-1β are not sensitive for, and the serum sIL-2R level is not specific for, CPMS. Therefore, measurement of these analytes will not be clinically useful for therapeutic or prognostic purposes in the majority of CPMS patients.

Acute optic neuritis: combined immunological markers and magnetic resonance imaging predict subsequent development of multiple sclerosis

The diagnostic significance of intrathecally synthesized IgG and virus-specific antibodies to measles, rubella and varicella-zoster (MRZ) in cerebrospinal fluid (CSF) remains controversial in cases of acute optic neuritis (AON). This study evaluates the prognostic value of baseline CSF and serum markers in AON, and correlates them with magnetic resonance imaging (MRI) and progression to multiple sclerosis (MS). Paired CSF and serum samples from 36 AON patients, 26 MS patients and 22 controls were analyzed for albumin, IgG, oligoclonal IgG (OI), MRZ antibodies, and blood-CSF barrier function; baseline MRI scanning of the head was also performed. The most sensitive parameter for detection of intrathecal inflammation in AON was OI (75%). Baseline MRI scans revealed abnormalities in 46% of the 28 patients with AON. Fifty percent of AON patients developed MS over the following 4 years. Ninety four percent of patients progressing to MS were positive for either OI, MRI or both. Of the AON patients initially positive for MRI and intrathecally-produced MRZ antibodies, 86% developed MS after 4 years. Only 17% of AON patients with negative results for OI and MRI developed MS. Six patients with abnormal OI but normal MRI progressed to MS. CSF and serum analyses, together with MRI, are the methods of choice for prognostic evaluation of patients with AON.

Autoimmune Thrombocytopenia Purpura

Autoimmune thrombocytopenia purpura (AITP) is a common haematological disorder caused by antiplatelet autoantibodies that lead to increased clearance of platelets by the reticuloendothelial system. Patients with AITP have low platelet counts and a bleeding tendency affecting the skin and mucosa. AITP can be classified into 2 main clinical syndromes: (a) idiopathic (primary or essential) thrombocytopenia (ITP) and (b) secondary AITP. Secondary AITP occurs in conjunction with a primary (usually autoimmune or malignant) disorder, and accounts for the majority of cases of AITP. ITP has an unknown aetiology, and diagnosis is made by exclusion of secondary AITP. Laboratory diagnosis of AITP relies on detection of platelet-associated immunoglobulin or on the demonstration of platelet autoantibodies that react with specific target antigens on the platelet surface. Treatment of AITP involves therapy with corticosteroids, followed if necessary by splenectomy. The use of high-dosage intravenous immunoglobulin G may improve the response to corticosteroids.

Dot-ELISA for serodiagnosis of human infections due to Western equine encephalitis virus☆

A standard dot-ELISA (enzyme-linked immunosorbent assay) was modified for use in detecting IgM and IgG class antibodies to Western equine encephalitis (WEE) virus in serum samples from humans infected with this virus. Nitrocellulose membranes were soaked in supernatant fluid from WEE virus-infected cell cultures, air dried, and blocked with bovine protein. Serum samples were pipetted onto sections of the nitrocellulose, incubated, and washed. Addition of antibody to human immunoglobulin conjugated to alkaline phosphatase and enzyme substrate were used to detect the antibodies. Of 13 samples positive for IgM antibody to WEE virus by IgM antibody capture ELISA, 12 were positive by IgM dot-ELISA. IgG antibody to WEE virus was detected by dot-ELISA in 7/8, 10/14 and 7/10 samples with neutralizing, hemagglutination-inhibiting, or complement-fixing antibodies, respectively.