Can a Saliva Test Provide a New Biomarker for MS?

PARIS—A noninvasive test that assesses immunoglobulin (Ig) free light chains in saliva may detect immunopathologic changes in the multiple sclerosis (MS) disease state and evaluate response to treatment, according to research presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. The technique has a specificity of 80% and sensitivity of 89% for diagnosing active MS, said lead author Esther Ganelin-Cohen, MD, PhD, Director of the Neuro-Immunology Clinic at Schneider Children’s Medical Center of Israel, Petach Tikva, Israel, on behalf of her research colleagues.

The complexity of MS requires different biomarkers to evaluate the various aspects of the disease. CSF analysis is commonly used, but the need for lumbar puncture makes CSF tests impractical for monitoring disease activity and response to treatment. In their search for noninvasive diagnostic methods, Dr. Ganelin-Cohen and colleagues hypothesized that Ig free light chain analysis in saliva may help detect immunopathologic changes in patients with MS. This assumption relied on prior reports indicating changes in mucosal immunity in patients with MS, and on a growing body of evidence for a potential diagnostic role of free light chains in MS.

A new technique based on Western blot analysis was developed to study kappa (k) and lambda (λ) free light chain monomers and dimers in saliva. Normal saliva showed high proportion of dimeric free light chains compared to that in the serum. “This finding might be explained by structural peculiarities of Ig in saliva,” Dr. Ganelin-Cohen said. “In contrast to most serum Ig, saliva IgA2 molecules incorporate the dimeric (not monomeric) light chains that may require production of larger amounts of dimeric light chains by the B cells synthesizing IgA2.”

Dr. Ganelin-Cohen and her colleagues compared free light chain monomer and dimer patterns in the saliva of patients with MS with those in healthy subjects. The intensity of the immunoreactive free light chain was measured, and the free light chain indices accounting for the total free light chain level and for monomer/dimer ratios (k monomer/dimer index and λ monomer/dimer index) were computed.

Most patients with active MS showed abnormally high free light chain levels, or a high proportion of monomeric free light chains. The reasons for such pathologic free light chain changes in patients with active MS are not clear, but they might be due to peripheral B lymphocytes penetrating oral mucosa and producing larger amounts of monomeric free light chains. Statistical analysis of these indices showed significant differences not only between patients with active MS (n = 27) and healthy subjects (n = 28), but also between patients with active MS (n = 27) and those in remission (n = 58).

Cut-off values were established to distinguish a healthy state from the pathologic conditions in MS: total free light chain level index = 17, k monomer/dimer index = 4.0, λ monomer/dimer index = 2.4. Most patients with active MS showed free light chain indices above these cut-off values.

The high specificity and sensitivity of the technique for diagnosing active MS enable this test to become a new noninvasive complementary tool to evaluate MS, Dr. Ganelin-Cohen and colleagues concluded.

PARIS—A noninvasive test that assesses immunoglobulin (Ig) free light chains in saliva may detect immunopathologic changes in the multiple sclerosis (MS) disease state and evaluate response to treatment, according to research presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. The technique has a specificity of 80% and sensitivity of 89% for diagnosing active MS, said lead author Esther Ganelin-Cohen, MD, PhD, Director of the Neuro-Immunology Clinic at Schneider Children’s Medical Center of Israel, Petach Tikva, Israel, on behalf of her research colleagues.

The complexity of MS requires different biomarkers to evaluate the various aspects of the disease. CSF analysis is commonly used, but the need for lumbar puncture makes CSF tests impractical for monitoring disease activity and response to treatment. In their search for noninvasive diagnostic methods, Dr. Ganelin-Cohen and colleagues hypothesized that Ig free light chain analysis in saliva may help detect immunopathologic changes in patients with MS. This assumption relied on prior reports indicating changes in mucosal immunity in patients with MS, and on a growing body of evidence for a potential diagnostic role of free light chains in MS.

A new technique based on Western blot analysis was developed to study kappa (k) and lambda (λ) free light chain monomers and dimers in saliva. Normal saliva showed high proportion of dimeric free light chains compared to that in the serum. “This finding might be explained by structural peculiarities of Ig in saliva,” Dr. Ganelin-Cohen said. “In contrast to most serum Ig, saliva IgA2 molecules incorporate the dimeric (not monomeric) light chains that may require production of larger amounts of dimeric light chains by the B cells synthesizing IgA2.”

Dr. Ganelin-Cohen and her colleagues compared free light chain monomer and dimer patterns in the saliva of patients with MS with those in healthy subjects. The intensity of the immunoreactive free light chain was measured, and the free light chain indices accounting for the total free light chain level and for monomer/dimer ratios (k monomer/dimer index and λ monomer/dimer index) were computed.

Most patients with active MS showed abnormally high free light chain levels, or a high proportion of monomeric free light chains. The reasons for such pathologic free light chain changes in patients with active MS are not clear, but they might be due to peripheral B lymphocytes penetrating oral mucosa and producing larger amounts of monomeric free light chains. Statistical analysis of these indices showed significant differences not only between patients with active MS (n = 27) and healthy subjects (n = 28), but also between patients with active MS (n = 27) and those in remission (n = 58).

Cut-off values were established to distinguish a healthy state from the pathologic conditions in MS: total free light chain level index = 17, k monomer/dimer index = 4.0, λ monomer/dimer index = 2.4. Most patients with active MS showed free light chain indices above these cut-off values.

The high specificity and sensitivity of the technique for diagnosing active MS enable this test to become a new noninvasive complementary tool to evaluate MS, Dr. Ganelin-Cohen and colleagues concluded.

PARIS—A noninvasive test that assesses immunoglobulin (Ig) free light chains in saliva may detect immunopathologic changes in the multiple sclerosis (MS) disease state and evaluate response to treatment, according to research presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. The technique has a specificity of 80% and sensitivity of 89% for diagnosing active MS, said lead author Esther Ganelin-Cohen, MD, PhD, Director of the Neuro-Immunology Clinic at Schneider Children’s Medical Center of Israel, Petach Tikva, Israel, on behalf of her research colleagues.

The complexity of MS requires different biomarkers to evaluate the various aspects of the disease. CSF analysis is commonly used, but the need for lumbar puncture makes CSF tests impractical for monitoring disease activity and response to treatment. In their search for noninvasive diagnostic methods, Dr. Ganelin-Cohen and colleagues hypothesized that Ig free light chain analysis in saliva may help detect immunopathologic changes in patients with MS. This assumption relied on prior reports indicating changes in mucosal immunity in patients with MS, and on a growing body of evidence for a potential diagnostic role of free light chains in MS.

A new technique based on Western blot analysis was developed to study kappa (k) and lambda (λ) free light chain monomers and dimers in saliva. Normal saliva showed high proportion of dimeric free light chains compared to that in the serum. “This finding might be explained by structural peculiarities of Ig in saliva,” Dr. Ganelin-Cohen said. “In contrast to most serum Ig, saliva IgA2 molecules incorporate the dimeric (not monomeric) light chains that may require production of larger amounts of dimeric light chains by the B cells synthesizing IgA2.”

Dr. Ganelin-Cohen and her colleagues compared free light chain monomer and dimer patterns in the saliva of patients with MS with those in healthy subjects. The intensity of the immunoreactive free light chain was measured, and the free light chain indices accounting for the total free light chain level and for monomer/dimer ratios (k monomer/dimer index and λ monomer/dimer index) were computed.

Most patients with active MS showed abnormally high free light chain levels, or a high proportion of monomeric free light chains. The reasons for such pathologic free light chain changes in patients with active MS are not clear, but they might be due to peripheral B lymphocytes penetrating oral mucosa and producing larger amounts of monomeric free light chains. Statistical analysis of these indices showed significant differences not only between patients with active MS (n = 27) and healthy subjects (n = 28), but also between patients with active MS (n = 27) and those in remission (n = 58).

Cut-off values were established to distinguish a healthy state from the pathologic conditions in MS: total free light chain level index = 17, k monomer/dimer index = 4.0, λ monomer/dimer index = 2.4. Most patients with active MS showed free light chain indices above these cut-off values.

The high specificity and sensitivity of the technique for diagnosing active MS enable this test to become a new noninvasive complementary tool to evaluate MS, Dr. Ganelin-Cohen and colleagues concluded.