The levels of an immunosuppressive protein called human leukocyte antigen G (HLA-G) are significantly higher in the immune cells of people with scleroderma or systemic lupus erythematosus (SLE), suggesting its potential role in controlling impaired immune responses in these diseases, a study has found.
However, further studies are required to clarify this protein’s role in disease development and progression, researchers say.
The study, “Expression of membrane-bound human leucocyte antigen-G in systemic sclerosis and systemic lupus erythematosus,” was published in the journal Human Immunology.
Scleroderma and SLE are inflammatory diseases characterized by the abnormal activation of the immune system and production of autoantibodies that wrongly attack the body’s own molecules and cells.
While they are distinct, scleroderma and SLE share some features, such as the involvement of interferon-mediated signaling, production of autoantibodies against molecules inside the cell’s nucleus, and increased tissue damage, including fibrosis (scarring).
HLA-G is a protein that regulates immune responses. Though best known for its involvement in maternal immune tolerance toward the fetus during pregnancy, it has also been associated with protective effects in inflammatory and autoimmune diseases.
Variants in the HLA-G gene — containing the instructions to produce the HLA-G protein — have been associated with an increased susceptibility to develop some immune-related diseases, including juvenile idiopathic arthritis.
However, the data is limited, and sometimes conflicting, about the levels of HLA-G in people with scleroderma and SLE.
The study included 48 systemic sclerosis (SSc) patients (38 women and 10 men, ages 38–89 ) — 34 with limited and 14 with diffuse scleroderma — and 24 people with SLE (all women, ages 27–69) followed at the clinical immunology unit of the University of Genoa, in Italy. A total of 43 age- and gender-matched healthy individuals were used as controls.
The team investigated HLA-G levels specifically at the cell surface of monocytes and three subtypes of T-cells: CD4 helper T-cells, which regulate inflammatory and immune responses of other immune cells; CD8 cytotoxic T-cells, which kill cancer and infected cells; and CD4/CD8 double-positive (DP) T-cells, whose function is still controversial.
Notably, the scientists said that these DP T-cells can be found in the skin of patients with early active scleroderma and may contribute to fibrosis, although they have been associated with suppressing autoantibody production in SLE.
Results showed similar proportions of immune cells between scleroderma patients and controls. In contrast, the proportion of helper T-cells was lower and that of cytotoxic T-cells was higher in the SLE group compared to controls (which is characteristic of the disease, the team said).
In both scleroderma and SLE patients, levels of HLA-G were significantly increased in monocytes and all three T-cell subtypes compared with those of the healthy individuals. Limited and diffuse scleroderma patients did not differ in their HLA-G levels.
Compared to those with SLE, people with scleroderma showed significantly higher HLA-G levels in monocytes and DP T-cells, and significantly lower levels in helper T-cells. HLA-G levels in cytotoxic T-cells were similar between the two groups.
These findings suggested “a potential role of HLA-G molecules in the complex immunological pathogenesis [disease-associated mechanisms] of these two autoimmune disorders,” the researchers wrote.
The increased levels of HLA-G in the cell membrane in immune cells “could reflect an attempt to control the immune derangement occurring in systemic autoimmune diseases,” they added.
“However, available data are inconclusive and further perspective basic and clinical investigations are required in order to define the role, if any, of HLA-G molecules in SSc [scleroderma] and SLE pathogenesis and clinical course,” the researchers said.
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