**1. Introduction**

Many environmental and occupational substances such as vinyl chloride, epoxy resins, solvents, pesticides, paraffin/silicone and silica particles cause dysregulation of autoimmunity [1, 2]. Silica-exposed patients suffer from silicosis (SIL), a condition that is well known to complicate with various autoimmune diseases [3, 4]. Of course, silica exposure produces typical

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pneumoconiosis [5, 6], which is defined as lung inflammation and fibrosis with scarring in the form of nodules in the middle to upper lungs. Although various clinical types such as acute, progressive and chronic SIL are distinguished depending on the exposed dosage of silica particles and duration, patients clinically exhibit dyspnea, fatigue, cough, chest pain and other pulmonary symptoms. There are several typical pulmonary complications such as pulmonary tuberculosis, tuberculous pleurisy, pneumothorax, bronchiectasis and lung cancer [7, 8].

titers of anti-Sjögren's-syndrome-related antigen A (SS-A) in SIL and SSc were higher than those of HV (**Figure 1B**). SS-A may be detected not only in Sjögren's syndrome, but also in other autoimmune diseases such as SSc and SLE. However, it may be interesting to note that SIL without any symptoms related to autoimmune diseases exhibited a higher titer for anti-SS-A Ab. Although clinical evaluation of anti-SS-A Ab in SIL has not been investigated, it is worth mentioning that SIL showed a pre-clinical status for autoimmune diseases as indicated by various epidemiological

Autoantibodies in Silicosis Patients: Silica-Induced Dysregulation of Autoimmunity

http://dx.doi.org/10.5772/intechopen.72999

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**Figure 1.** Comparison of titers for anti-nuclear antibody (ANA), anti-SS-A antibody (Ab), anti-CENP-B Ab and anti-Scl-70 Ab among healthy volunteers (HV), silicosis cases (SIL) and patients with systemic sclerosis (SSc). Except for ANA, titers are shown as logarithmic values. Statistical significance was examined using the student T-test and p < 0.05

was defined as significant. All titers were measured using a multiplex ELISA kit for ANA.

studies [9–17].

In addition to these lung complications, it is well known that the condition of SIL patients is often complicated with autoimmune diseases. The classical disease is known as Caplan's syndrome, complicated with rheumatoid arthritis (RA) [9]. The initial description reported by Caplan involved 51 cases among coal miners. Thereafter, many epidemiological reports revealed high odds ratios for the occurrence of RA in SIL [10, 11]. Furthermore, other autoimmune diseases such as systemic sclerosis (SSc) [12, 13], systemic lupus erythematosus (SLE) [14, 15] and anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis/nephritis [16, 17] have been reported in case reports and epidemiological investigations.

We have been studying the direct effects of silica particles on human lymphocytes, especially responder T (Tresp) and regulatory T (Treg) cells [18–20], as well as investigating autoantibodies found in SIL [21–28]. In this chapter, clinical evaluation, epitope search and functional assays of several autoantibodies found in SIL are described and mechanistic analyses of T cells exposed to silica particles are conducted.
