Elevated serum level of interleukin-32α in the patients with myasthenia gravis

Abstract

A new cytokine, interleukin-32 (IL-32), has been implicated in the pro-inflammatory immune responses in several autoimmune disorders, such as rheumatoid arthritis and inflammatory bowel diseases. Myasthenia gravis (MG) is a well-characterized autoimmune disease directed at the postsynaptic acetylcholine receptor (AChR) or end plate of the neuromuscular junction. IL-32 is a cytokine that induces tumor necrosis factor (TNF)-α, IL-6, IL-1β, and chemokine. IL-6, TNF-α, and IL-2 are related to the pathogenesis and immunoregulation of MG. The gene expression of IL-32 is increased in human natural killer (NK) cells and T lymphocytes when stimulated by IL-2 or mitogen. NK cells influence the development of experimental autoimmune MG (EAMG) and possibly MG. The aim of this study was to examine whether IL-32α levels are increased in patients with MG and to investigate the relationship between IL-32α levels and disease activity in human MG. Serum IL-32α levels were significantly higher in the MG patients (p = 0.03): 460.07 ± 192.30 pg/mL in MG patients and 248.45 ± 188.42 pg/mL in the healthy control group. Although there was no significant statistical difference, serum IL-32α levels of patients with both anti-AChR binding and blocking antibodies trended to be higher than those without either antibodies (521.56 ± 212.92 pg/mL vs. 339.52 ± 182.78 pg/mL, p = 0.16). IL-32α serum levels tended to decrease with clinical improvement in generalized MG. This study suggests the possibility that IL-32 might contribute to MG pathogenesis or immunoregulation.

Interleukin-32 Gamma Stimulates Bone Formation by Increasing miR-29a in Osteoblastic Cells and Prevents the Development of Osteoporosis

“…However, there is insufficient information to know the physiological relevance of systemic levels of IL-32γ in pathogenesis. Even though the concentration of α-isoform is elevated in the blood of patients with chronic obstructive pulmonary disease48, myasthenia gravis49, and stomach cancer50, the clinical meaning of high blood levels of IL-32α in patients with various diseases is still obscure. In addition, the pathogenic deterioration seen in RA and AS cases is caused by abnormal local accumulation of IL-32γ in inflamed tissues, with no considerable difference between patients’ blood and that of a healthy population202122.…”

IL-32 Promotes Angiogenesis

“…IL-32 is present in increased abundance in a variety of diseases, including chronic obstructive pulmonary disease (10), inflammatory bowel disease and psoriasis (11), allergic rhinitis (12), and myasthenia gravis (13), and its levels are directly related to disease severity in rheumatoid arthritis (14, 15). …”

Clinical significance of detection of antibodies to fetal and adult acetylcholine receptors in myasthenia gravis

“…Group I: OMG patients in whom weakness was exclusive to the eyelids and extraocular muscles and did not progress to GMG within the first 2 years. Group II: patients with GMG (disease affecting muscles besides ocular muscles) [8,14] . According to the symptoms at disease onset, patients in Group II were further divided into two subgroups.…”

“…Up to 80% of patients who present with ocular manifestations develop generalized muscle weakness within 2 years [4–6] . However, in some patients, the symptoms are restricted to the ocular muscles for more than 2 years, and this is defined as ocular myasthenia gravis (OMG) [7,8] . A previous study showed that the presence of anti-AChR antibody is associated with an increased risk of secondary generalization of muscular weakness [9] .…”