key: cord-328271-ma3s7hrs
authors: Madden, David L.; Mundon, Francis K.; Tzan, Nancy R.; Fuccillo, David A.; Dalakas, Marinos C.; Calabrese, Vincent; Elizan, Tenesita S.; Román, Gustavo C.; Sever, John L.
title: Antibody to human and simian retrovirus, HTLV‐I, HTLV‐II, HIV, STLV‐III, and SRV‐I not increased in patients with multiple sclerosis
date: 2004-10-08
journal: Ann Neurol
DOI: 10.1002/ana.410230738
sha: 
doc_id: 328271
cord_uid: ma3s7hrs

We have tested sera from patients with multiple sclerosis, matched controls, and those with other neurological diseases, as well as sera from patients with the acquired immunodeficiency syndrome and controls and patients with tropical spastic paraparesis (TSP) and controls for antibody to human T‐lymphotropic virus type I (HTLV‐I), HTLV‐II, human immunodeficiency virus (HIV), simian T‐lymphotropic virus type III, or simian retrovirus type I by immunofluorescent activity test, and for HTLV‐I and HIV by the ELISA method. Sera from patients with multiple sclerosis and matched controls, and from patients with optic neuritis and Parkinson's or other neuromuscular diseases did not have antibody to any of the retroviruses tested. Specimens from TSP patients and some controls contained HTLV‐I antibody. We conclude from our study that only TSP patients had serological evidence of infection with one of the retroviruses studied.

We 

The None of the ELSA HIV OD readings on the samples from MS patients, patients with optic neuritis, controls, and patients with other neurological disease were above the cutoff of 0.39. An analysis of the OD readings obtained did not indicate that the readings were higher in the MS patients as compared to the controls.

Seventeen of the 20 TSP patients had HTLV-I ELISA OD readings above the cutoff of 0.36; 2 patients with other neurological disease also had readings above the cutoff. Three of the patients with clinical TSP, 5 with other neurological diseases, and the 9 controls had ELISA OD readings below the 0.36 S172 Annals of Neurology Supplement to Volume 23, 1788 cutoff and were considered negative. None of the HTLV-I ELISA readings on samples from AIDS patients or controls or from MS patients, patients with optic neuritis, contro1s, and patients with other neurological diseases were above the cutoff of 0.36.

Analysis of the OD readings obtained did not indicate that the readings were higher in the MS patients as compared to the controls.

Retroviruses have been associated with neurological disease in patients with AIDS and with TSP. The clinical signs and symptoms of TSP resemble, to some extent, MS. In our study of serum samples collected before HIV infection became prevalent in the United States, we could not demonstrate a serological relationship between the human or simian retroviruses and MS.

Several explanations for the differences of these findings and those reported by Koprowski and colleagues [17 are evident. First, it is possible that some patients in Key West have HTLV-I antibody because it is a tropical island on the edge of the TSP Caribbean belt. Second, modern society being so mobile, individuals who have lived or traveled to HTLV-I-endemic regions may develop antibody, return to more northern latitudes, and later develop MS independent of their HTLV-I status. Further, it should be expected that MS patients have lifestyles that are similar to the general population. Some will develop HIV antibody as a result of homosexual activity, heterosexual transfer, intravenous drug usage, and transfusion. Careful questioning may identify these individuals.

It has been suggested that the type of test used may influence the results. Koprowski [personal communication) believes that there is insufficient antigen on commercial plates to detect the possible cross-reactions with yet unidentified retrovirus. He believes that one must greatly overload the plates with antigen to identlfy the possible cross-reacting antibodies. Data from the use of commercial kits indicated that such kits are constructed to be overly sensitive; they identify 1 to 3% of false positives in order not to miss any true positives. Our laboratory has had experience in developing many ELISA tests for serological studies. We find it necessary to titrate the antigen and conjugate with positive and negative serum to get the right concentration of each to ensure maximum sensitivity and specificity. Altering one parameter, such as increasing antigen concentration, may increase nonspecificity and false-positive reaction. IFA is useful in confirming HTLV-I antibody and, by use of proper cell control, in detecting nonspecificity.

We conclude from our study that our MS patients did not have serological evidence of retrovirus infection. It is possible for some MS patients to have retrovirus antibody that is not related to MS. During the past 10 years, more than ten different possible agents have been suggested as causes of MS [27. Among these are a number of recognized viruses, such as measles, canine distemper, scrapie agent, and coronaviruses, and multiple sclerosis-associated agents of unclear classification, the bone marrow agent, and the chimpanzee agent. The serological evidence for etiological association of a retrovirus with MS seems weaker than that available for measles, rubella, and coronavirus.

Multiple sclerosis and human T-cell lymphotropic retroviruses

Search for the cause of multiple sclerosis and other chronic diseases of the central nervous system