The Worm Turns for the Better in MS Patients

BUENOS AIRES, Jan. 17 – For patients with relapsing-remitting multiple sclerosis, acquiring a helminth infection might be something of a lucky break, investigators here suggested.

In a small observational study, those with confirmed relapsing-remitting MS who also had parasitic worm infections showed significantly fewer MS exacerbations, minimal variations in disability scores, and fewer changes on MRI than did non-infected patients, reported Jorge Correale, M.D., and Mauricio Farez, M.D., of the Raul Carrea Institute for Neurological Research, and colleagues.

Parasitic infections may alter the course of MS by spurring increased production of anti-inflammatory and antiproliferative cytokines and regulatory T cells, a finding that could point the way to targeted immunologic therapies for MS, the authors speculated in the January issue of Annals of Neurology.

"These findings provide evidence to support autoimmune downregulation secondary to parasite infections in MS patients through the action of regulatory cells whose effects extend beyond the response to the invading agent," they wrote.

Parasitic infections may prompt the generation of new regulatory T cells, or enhance the activity or expansion of existing cells, or both.

The finding may also explain why the prevalence of MS is low in areas where parasitic infections are endemic, and why there is a higher prevalence of autoimmune diseases in developed countries, the authors suggested.

They likened this to the "hygiene hypothesis" of allergy and asthma, which holds that immune systems of people in developed countries live in cleaner environments and never learn to become tolerant to environmental allergens, and therefore mount an overzealous attack when they encounter dust, molds, and pollen.

"During recent decades, strong epidemiological evidence has accumulated indicating a steady increase in autoimmune disease incidence in developed countries," they wrote. "In addition, differences in autoimmune disease prevalence have also been observed between rural and urban areas within the same country. Because this epidemiological shift occurs in a timeframe too short to be attributable to genetic factors, it is believed that environmental factors could account for changes in the immune repertoire."

To test this theory, the authors followed 12 patients with confirmed relapsing-remitting MS and eosinophilia, a sign of parasitic infection. Parasitic infections were confirmed through stool samples. The patients were compared with 12 uninfected MS patients matched for age, gender, and disease duration, and with 12 healthy controls.

Of the patients with parasitic infections, three were infected with dwarf tapeworm (Hymenolepis nana), three with roundworm (Trichuris trichuria), three with nematodes (Ascaris lumbricoides), two with threadworm (Strongyloides stercoralis), and one with pinworm (Enterobius vermicularis).

The patients were entered into the study when their eosinophil counts became elevated, and were given a comprehensive neurological exam every three months, with additional visits scheduled within 72 hours of relapses. Immunological exams were carried out during the last 12-18 months of the study.

The investigators evaluated peripheral blood mononuclear cells (PBMCs) for production of the cytokines interleukins-4, -10, -12, transforming growth factor beta (TGF-), and γ-interferon. They also used polymerase chain reaction for genes controlling regulatory T-cell transcription factors, including FoxP3 and Smad7.

The authors found that during 4.6 years of follow-up, the MS patients with the helminth infections had a total of three relapses, with nine in this group having no relapses. In contrast, there were 56 relapses among 10 of 12 worm-free MS patients.

In addition, six infected patients had new enlarging MS lesions on MRI and six had no new lesions, whereas all uninfected patients had new lesions, with a total of 164 new or enlarging lesions.

Two of the 12 infected patients showed minimal Expanded Disability Status Score changes, which lasted less than three months. In contrast, 11 uninfected patients showed an overall increase in the scores over baseline.

They also found that infected patients had significantly higher levels of suppressor cytokines compared with uninfected MS patients.

Since MS involves an inflammatory response associated with the production of certain regulatory proteins known as cytokines, the number of cells producing cytokine suppressants was measured and found to be significantly higher in infected patients.

Specifically, infected patients had significantly increased levels of IL-10 and TGF-, and significantly decreased levels of IL-12 and interferon-γ-secreting cell. Additionally, the cloning frequency of regulatory T cells and transcription factors were significantly higher among helminth-infected patients compared with uninfected patients.

"Parasites inhabit immune-competent hosts for long periods and can therefore develop modulatory molecules generating strong anti-inflammatory responses destined to enhance their survival," Dr. Correale and Dr. Farez wrote. "Further investigation is warranted to identify which molecules cause immunomodulatory effects that dampen inflammatory reactions normally occurring in autoimmune diseases."

Primary source: Annals of Neurology
Source reference:
Correale J and Farez M. "Association between Parasite Infection and Immune Responses in Multiple Sclerosis." Ann Neurol 2007.61;1.