Environmental triggers of autoimmune thyroiditis

Abstract

Autoimmune thyroiditis is among the most prevalent of all the autoimmunities. Autoimmune thyroiditis is multifactorial with contributions from genetic and environmental factors. Much information has been published about the genetic predisposition to autoimmune thyroiditis both in experimental animals and humans. There is, in contrast, very little data on environmental agents that can serve as the trigger for autoimmunity in a genetically predisposed host. The best-established environmental factor is excess dietary iodine. Increased iodine consumption is strongly implicated as a trigger for thyroiditis, but only in genetically susceptible individuals. However, excess iodine is not the only environmental agent implicated as a trigger leading to autoimmune thyroiditis. There are a wide variety of other synthetic chemicals that affect the thyroid gland or have the ability to promote immune dysfunction in the host. These chemicals are released into the environment by design, such as in pesticides, or as a by-product of industry. Candidate pollutants include polyaromatic hydrocarbons, polybrominated biphenols, and polychlorinated biphenols, among others. Infections are also reputed to trigger autoimmunity and may act alone or in concert with environmental chemicals. We have utilized a unique animal model, the NOD.H2(h4) mouse to explore the influence of iodine and other environmental factors on autoimmune thyroiditis.

Figure 1

Thyroid glands from NOD.H2^h4 mice. A. normal unaffected gland from an untreated mouse. B. Infiltrated gland (+4) after 8 weeks of treatment with excess iodine in the drinking water.

Figure 2

Dose response of NaI concentration and thyroid lesions in NOD.H2^h4 mice born and bred in conventional housing. The thyroids are graded on H and E stains from paraffin sections. Six to 8 sections of tissue are examined. Two independent readers evaluate the tissue. The thyroids are scored for infiltration by the following criteria:

1. 0 = no infiltration,

2. 1+ = infiltration in <20% of the gland,

3. 2+ = infiltration from 20–30% of the gland,

4. 3+ = infiltration from 30–50% of gland,

5. 4+ >50% infiltration of gland

Figure 3

Combined results of three transfer experiments. All donors received 0.15% NaI water for at least 8 weeks. Spleen cells were cultured for 3 days with 25 ug/ml of mouse thyroglobulin. Transfer group recipients (n=63) received low dose iodine (0.005%w/v) two weeks prior to transfer of spleen cells given i.v. Control mice (n=69) similarly on low dose iodine received PBS instead of cells. Thyroids were assessed for lymphocytic infiltration 14 days after transfer. Conclusions: Thyroiditis can be transferred in this model using spleen cells from mice fed with iodine.

Figure 4

Frequency of thyroiditis in untreated NOD.H2^h4 mice housed in conventional (Con) or specific pathogen free (SPF) conditions. A. Mice housed in conventional conditiions developed earlier and more severe thyroiditis ( R²= 0.45 than B. NOD.H2h4 mice born and reared under SPF conditions (R²=0.054). Both groups showed increased frequency of thyroiditis with age.

Figure 5

Prevalence of thyroiditis in female breeder (+B) or non-breeder (NonB) NOD.H2^h4 mice born and raised in conventional (Con) or specific pathogen free (SPF) conditions. Both breeder and non-breeder groups raised in conventional conditions had a higher frequency of thyroiditis than their SPF counterparts. Conventionally raised breeder mice showed significantly greater thyroiditis over breeder mice raised under SPF conditions (p<0.03, Fisher’s exact test).