Lab evaluation for environmental triggers and autoimmune disease

There are multiple pathways to autoimmunity, said Aristo Vojdani, PhD, MDC, CLS, at the 2018 Institute for Functional Medicine (IFM) Annual International Conference. In fact, the immune system evolved multiple mechanisms for controlling self-reactivity, and defects in one or more of these mechanisms can lead to a breakdown of tolerance.

These pathways include:

  • Failure in oral tolerance
  • Inefficiency of central tolerance
  • Breakdown of peripheral tolerance
  • Recognition of self RNA or DNA by innate cells
  • Disturbance in the gut bacterial ecosystem
  • Non-coding RNAs, including microRNAs and IncRNAs
  • Sex bias in autoimmunity

For the purposes of his presentation, Vojdani focused on three major mechanisms of protection against autoimmunity:

  1. Oral tolerance
  2. Central tolerance
  3. Peripheral tolerance

Oral tolerance is the state of active inhibition of the immune responses to an antigen through the oral route. Central tolerance, on the other hand, is the process of eliminating any developing T cells or B cells that are reactive to self. Finally, peripheral tolerance provides a second level of control to restrain potentially autoreactive

Failure in oral tolerance can result in enhanced intestinal permeability to large molecules and many autoimmune disorders. Defective thymic expression of a single molecule is sufficient to induce an autoimmune response to multiple organs. Failure can result in autoreactive T cells initiating potentially dangerous immune responses against the body’s own tissues or against harmless materials such as food or commensal organisms.

There are a few different transcription factors of T helper cells, which play a role in autoimmune disease. These include:

  • FOXP3 transcription factor
  • RORĘ“T transcription factor
  • CD28 ICOS
  • T-Bet transcription factor
  • GATA transcription factor

When T-helper cells are over activated, they become inflamed and irritated, which can cause an autoimmune reaction, said Vojdani. To measure and test for autoimmunity, he suggested a few basic tests. For connective tissue disease, this includes anti-nuclear antibody (ANA), extractable nuclear antigen (ENA), double-stranded DNA (dsDNA), small nuclear ribonucleoprotein (snRNP), ribonucleoprotein (RNP), topoisomerase (Scl-70), histidyl-tRNA synthetase (Jo1), and immune complexes. For gastric autoimmunity, Vojdani recommends gastric parietal cell antibody and intrinsic factor antibody. For inflammatory bowel disease, test anti-saccharomyces cerevisiae antibody (ASCA) and, for ulcerative colitis/vasculitis, test anti-neutrophil cytoplasmic antibody (ANCA).

Tests for primary biliary cirrhosis include actin antibody, liver kidney microsomal antibody, and mitochondrial antibody. For rheumatology, look at rheumatoid factor (RF), antu-cyclic citrullinated protein antibody, and anti-carbamylated proteins. For phospholipid syndrome, look at anti-cardiolipin, anti-β2 glycoprotein 1, and anti-phosphatidylserine.

Thyroid autoimmunity is identifiable through a number of tests, including anti-thyroid peroxidase antibody, anti-thyroid thyroglobulin antibody, anti-thyroid stimulating hormone receptor antibody, anti-thyrotropin receptor antibody, anti-thyroxine antibody, anti-thyroxine deiodinase antibody, anti-triiodothyronine antibody, anti-thyroid binding globulin antibody, anti-thyrotropin binding inhibitory immunoglobulin antibody, and anti-sodium/iodine symporter antibody.

All of these tests can help practitioners evaluate immune function and detect inflammation. However, it isn’t enough to say a patient has an autoimmune disease. “Look at the pattern the patient is having under a microscope,” said Vojdani.

The four factors that contribute to autoimmune disease include genetics, toxic chemicals, infections and bacteria, and dietary components. The etiology of autoimmune diseases is due to a combination of genetic predisposition and environmental factors that alter the expression of immune regulatory genes through various mechanisms including epigenetics. The presence of autoantibodies has been detected in most, but not all, autoimmune diseases before the appearance of clinical symptoms.

In some cases, the presence or levels of these autoantibodies portends not only the risk of developing a corresponding autoimmune disease, but occasionally the severity as well. This observation is intriguing because it suggests that we can, to some degree, predict who may or may not develop autoimmune diseases, Vojdani said.

However, as complex as autoimmune diseases can be, practitioners must strive to uncover the true causes of a patients’ condition, in order to recommend the most appropriate solution. Vojdani encouraged practitioners to find the root cause, the “why” in terms of autoimmune disease.

“It is not enough to say the patient has [a condition] and put them on a course of treatment,” he said. “Ask why, go to the literature, and address the underlying cause of autoimmune disease.”

Editor’s note: This article is part of Integrative Practitioner’s live coverage of the Institute of Functional Medicine’s 2018 Annual International Conference. For a full list of coverage, click here.