B-cells in Skin of Scleroderma Patients May Predict Disease Progression

The presence of B-cells — a type of white blood cell — in the skin of scleroderma patients may predict a more aggressive disease and worsening of skin fibrosis, a study shows.

The study, “Characterization of inflammatory cell infiltrate of scleroderma skin: B cells and skin score progression,” was published in the journal Arthritis Research & Therapy.

High numbers of specific types of white blood cells like T-cells and macrophages, which fight infections and regulate inflammatory processes, often are found in the skin of scleroderma patients and are involved in the development of fibrosis (scarring) that occurs in this condition.

Increasing evidence also suggests the involvement of B-cells, the white blood cells that produce antibodies to fight against foreign substances. However, while high numbers of B-cells have been found in scleroderma patients, their presence in skin affected by scleroderma is still not well-defined.

To clarify the type of immune cell present in the skin of these patients, and the potential role of B-cells in skin fibrosis, researchers analyzed samples from clinically affected and unaffected skin from patients with scleroderma and the skin of healthy individuals.

The study included skin samples from 28 scleroderma patients (24 women and four men) with a mean age of 44.6 years, and four healthy women, aged 36-55 years, as controls. Two skin samples were collected from each scleroderma patient: one from an affected area (forearm), and another from an unaffected area (buttock).

Twenty patients (71.4%) had diffuse systemic scleroderma — a severe form of scleroderma, with extensive skin fibrosis — and 19 patients (67.9%) had early disease; nine patients (32.1%) had long-standing disease.

Skin samples were examined for the presence of T-cells, macrophages, B-cells, and plasma B-cells — the mature form that actively produces antibodies. Patients were followed-up by a mean of 6.5 months, and a change higher than 20% in the Rodnan skin score  (a standard measure of skin fibrosis in scleroderma) was considered to indicate significant disease progression.

Researchers found that T-cells and macrophages were present in all skin samples from scleroderma patients, and that their numbers were significantly higher in clinically affected skin than in unaffected skin, supporting their role in the development of fibrosis.

B-cells were found in the skin of 17 patients (60.7%): in both skin samples in nine patients, in affected skin samples in seven patients, and in unaffected skin in one patient. Plasma B-cells were present in all affected skin samples and in 89.3% of unaffected skin.

The greater numbers of B-cells in affected skin samples were associated with early scleroderma, compared to patients with long-standing disease, and the presence of B-cells in unaffected skin was found only in patients with diffuse scleroderma.

Importantly, researchers noted, none of these B-cell subtypes were found in healthy skin samples, suggesting that their presence is characteristic of skin in scleroderma.

After six months, seven patients had significant disease progression, and all of them had shown B-cells in their skin samples, suggesting that the presence of B-cells in the skin may be used as a biomarker to predict disease progression.

“Among the various immune cells, B-cells appear to be the only ones linked to progression of skin involvement over time,” the researchers wrote.

The team added that therapeutic strategies to decrease the number of skin B-cells or their function “might prove useful in the management of cutaneous [skin] involvement in SSc [scleroderma] from the earliest phases of the disease.”