Chapter 18 - Construction of bioscore for detection of self-tolerance failure: From analysis of silicosis cases

Abstract

Silicosis (SIL) is a well-known typical lung fibrosis categorized as pneumoconiosis. Patients suffer from dyspnea, shortness of breath, cough and sputum, which can develop into respiratory failure. The main complications of silicosis are pulmonary diseases. However, SIL is often complicated with various autoimmune diseases such as rheumatoid arthritis, systemic sclerosis, and anti-neutrophil cytoplasmic antibody (ANCA)-related vasculitis. We have been investigating the cellular and molecular alterations of immune cells derived from SIL as well as silica particles in vitro with particular emphasis on the effects on human immune cells. Results showed continuous activation and long survival of CD4 + responder T (Tresp) cells. Additionally, CD4 + 25 + regulatory T (Treg) cells were lost by earlier apoptosis since CD95/Fas death receptor was overexpressed as a result of chronic activation induced by silica particles. The imbalance between Tresp and Treg cells may be the basis for the alteration of dysregulation in autoimmunity. Then, we developed an autoimmune score (AIS) by multiple regression analysis using 19 immune factors in plasma of 19 healthy volunteers (HV) and 20 SIL patients who did not show any autoimmune clinical symptoms. The formula generated is [AIS = (0.119 × sFas) + (1.063 × IgG4) + (0.059 × IL-6) + 0.063]. Using this formula, all values from the 19 HV and 20 SIL patients ranged between 0.90 and 2.71. If we set the cut off value as 1.3935, HV and SIL patients were clearly divided, with only one false-negative SIL patient. We could use this formula for early preclinical detection of autoimmune diseases among various populations predominantly comprising relatively young and female subjects. There are presently some limitations to this formula, such as age differences between two groups and the use of limited factors. Thus, an altered version of this formula could be proposed to be used in the fields of preventive medicine.