Interferon Pathway May Lead to Biomarker of Lupus Severity

Activation of the interferon-α pathway identifies a subgroup of lupus erythematosus patients with distinct serologic features and more active disease, according to Kyriakos A. Kirou, M.D.

There is no consensus in the current literature regarding the most useful or accurate marker of lupus disease activity, thus the use of increased interferon-inducible gene expression as a potential biomarker of active disease could prove valuable to clinicians and researchers.

The investigators subjected freshly isolated peripheral blood mononuclear cells from 77 patients with systemic lupus erythematosus (SLE), 22 disease controls with either rheumatoid arthritis or inflammatory uveitis, and 28 healthy donors to real-time polymerase chain reaction for three genes (PRKR, IFIT1, and IF144) that are preferentially induced by interferon-α. The results were used to determine an IFN-α score for all participants.

SLE patients with a high IFN-α score had a significantly higher prevalence of renal disease, a greater number of American College of Rheumatology criteria for SLE, and a higher Systemic Lupus International Collaborating Clinics damage index (SDI) score than did patients with a low IFN-α score (Arthritis Rheum. 2005;52:1491–503).

Patients with high IFN-α scores also showed increased disease activity, as measured by lower serum C3 levels, hemoglobin levels, absolute lymphocyte counts, and albumin levels, and a higher anti-double-stranded DNA (dsDNA) titer, erythrocyte sedimentation rate, and SLE Disease Activity Index 2000 score.

“Our most striking data, and that which may provide us new clues regarding underlying disease mechanisms, came from analysis of the serologic profiles of the SLE patients,” wrote Dr. Kirou and colleagues at the Hospital for Special Surgery in New York.

The investigators found that the presence of antibodies specific for RNA-binding protein (RBP), including Ro, U1 ribonucleoprotein (RNP), and Sm, was significantly associated with a high IFN-α score.

Logistic regression analysis confirmed that the presence of renal disease, low complement levels, autoantibodies specific for RBP (but not anti-dsDNA or antiphospholipid autoantibodies), and higher SDI scores, all independently increased the likelihood of having a high IFN-α score.

“Activation of the IFN-α pathway could be an important mediator of the immune system alterations that confer tissue damage in SLE,” the authors wrote.

Additionally, activation of the IFN-α pathway may also contribute to production of pathogenic autoantibodies by direct and indirect effects on B cells, resulting in differentiation and Ig class switching to IgG and IgA isotypes.

Prospective longitudinal studies are needed to assess the role of interferon-inducible genes in monitoring disease activity, they concluded.

Activation of the interferon-α pathway identifies a subgroup of lupus erythematosus patients with distinct serologic features and more active disease, according to Kyriakos A. Kirou, M.D.

There is no consensus in the current literature regarding the most useful or accurate marker of lupus disease activity, thus the use of increased interferon-inducible gene expression as a potential biomarker of active disease could prove valuable to clinicians and researchers.

The investigators subjected freshly isolated peripheral blood mononuclear cells from 77 patients with systemic lupus erythematosus (SLE), 22 disease controls with either rheumatoid arthritis or inflammatory uveitis, and 28 healthy donors to real-time polymerase chain reaction for three genes (PRKR, IFIT1, and IF144) that are preferentially induced by interferon-α. The results were used to determine an IFN-α score for all participants.

SLE patients with a high IFN-α score had a significantly higher prevalence of renal disease, a greater number of American College of Rheumatology criteria for SLE, and a higher Systemic Lupus International Collaborating Clinics damage index (SDI) score than did patients with a low IFN-α score (Arthritis Rheum. 2005;52:1491–503).

Patients with high IFN-α scores also showed increased disease activity, as measured by lower serum C3 levels, hemoglobin levels, absolute lymphocyte counts, and albumin levels, and a higher anti-double-stranded DNA (dsDNA) titer, erythrocyte sedimentation rate, and SLE Disease Activity Index 2000 score.

“Our most striking data, and that which may provide us new clues regarding underlying disease mechanisms, came from analysis of the serologic profiles of the SLE patients,” wrote Dr. Kirou and colleagues at the Hospital for Special Surgery in New York.

The investigators found that the presence of antibodies specific for RNA-binding protein (RBP), including Ro, U1 ribonucleoprotein (RNP), and Sm, was significantly associated with a high IFN-α score.

Logistic regression analysis confirmed that the presence of renal disease, low complement levels, autoantibodies specific for RBP (but not anti-dsDNA or antiphospholipid autoantibodies), and higher SDI scores, all independently increased the likelihood of having a high IFN-α score.

“Activation of the IFN-α pathway could be an important mediator of the immune system alterations that confer tissue damage in SLE,” the authors wrote.

Additionally, activation of the IFN-α pathway may also contribute to production of pathogenic autoantibodies by direct and indirect effects on B cells, resulting in differentiation and Ig class switching to IgG and IgA isotypes.

Prospective longitudinal studies are needed to assess the role of interferon-inducible genes in monitoring disease activity, they concluded.

Activation of the interferon-α pathway identifies a subgroup of lupus erythematosus patients with distinct serologic features and more active disease, according to Kyriakos A. Kirou, M.D.

There is no consensus in the current literature regarding the most useful or accurate marker of lupus disease activity, thus the use of increased interferon-inducible gene expression as a potential biomarker of active disease could prove valuable to clinicians and researchers.

The investigators subjected freshly isolated peripheral blood mononuclear cells from 77 patients with systemic lupus erythematosus (SLE), 22 disease controls with either rheumatoid arthritis or inflammatory uveitis, and 28 healthy donors to real-time polymerase chain reaction for three genes (PRKR, IFIT1, and IF144) that are preferentially induced by interferon-α. The results were used to determine an IFN-α score for all participants.

SLE patients with a high IFN-α score had a significantly higher prevalence of renal disease, a greater number of American College of Rheumatology criteria for SLE, and a higher Systemic Lupus International Collaborating Clinics damage index (SDI) score than did patients with a low IFN-α score (Arthritis Rheum. 2005;52:1491–503).

Patients with high IFN-α scores also showed increased disease activity, as measured by lower serum C3 levels, hemoglobin levels, absolute lymphocyte counts, and albumin levels, and a higher anti-double-stranded DNA (dsDNA) titer, erythrocyte sedimentation rate, and SLE Disease Activity Index 2000 score.

“Our most striking data, and that which may provide us new clues regarding underlying disease mechanisms, came from analysis of the serologic profiles of the SLE patients,” wrote Dr. Kirou and colleagues at the Hospital for Special Surgery in New York.

The investigators found that the presence of antibodies specific for RNA-binding protein (RBP), including Ro, U1 ribonucleoprotein (RNP), and Sm, was significantly associated with a high IFN-α score.

Logistic regression analysis confirmed that the presence of renal disease, low complement levels, autoantibodies specific for RBP (but not anti-dsDNA or antiphospholipid autoantibodies), and higher SDI scores, all independently increased the likelihood of having a high IFN-α score.

“Activation of the IFN-α pathway could be an important mediator of the immune system alterations that confer tissue damage in SLE,” the authors wrote.

Additionally, activation of the IFN-α pathway may also contribute to production of pathogenic autoantibodies by direct and indirect effects on B cells, resulting in differentiation and Ig class switching to IgG and IgA isotypes.

Prospective longitudinal studies are needed to assess the role of interferon-inducible genes in monitoring disease activity, they concluded.