New markers, criteria promote earlier intervention in juvenile lupus

BUENOS AIRES – A group of new studies on juvenile-onset systemic lupus erythematosus suggests that investigators are gaining a foothold on noninvasively monitoring renal disease, making more accurate diagnoses, and determining the prevalence of hippocampal atrophy in adolescents with the condition.

One of the three reports presented at the international congress on systemic lupus erythematosus (SLE) involved research from U.K. investigators on novel noninvasive biomarkers that can predict the course of renal disease in juvenile SLE, potentially allowing for earlier intervention, fewer kidney biopsies, and more accurate drug titration.

Researchers from Argentina revealed that new classification criteria for SLE, published in 2012, were more sensitive and specific in juvenile lupus patients than the widely used American College of Rheumatology criteria, which were last revised in 1997.

A third report from Brazil-based investigators found that atrophy of the hippocampus, the part of the brain associated with memory and learning, occurred in nearly two-thirds of a cohort of juvenile SLE patients.

Urine biomarkers for lupus nephritis

Dr. Louise Watson of Alder Hey Children’s NHS Hospital, Liverpool, England, presented findings on novel urine biomarkers from a multicenter, prospective cohort study of 64 SLE patients aged 16 years and younger. "We were keen to look for better ways to monitor the disease through biomarkers, and to move from a more reactive to a more proactive approach," Dr. Watson said at the meeting.

Rather than wait until the onset of proteinuria to start treatment, reliable noninvasive biomarkers "could allow disease to be detected at a much earlier time point, and hopefully help us try and prevent some of the irreversible kidney damage that we might see" associated with juvenile-onset SLE.

Dr. Watson and her colleagues looked at both standard and novel biomarkers in the cohort, and found that two novel ones – monocyte chemoattractant protein 1 (MCP1) and neutrophil gelatinase associated lipocalin (NGAL) – predicted changes in the course of renal disease over a 2-year period. MCP1 was highly predictive of disease improvement, and NGAL of disease progression.

MCP1 at a concentration of 343 pg/mL was a significant predictor of improvement in renal disease (P = .013; specificity 71%, sensitivity 70%), the researchers found. Meanwhile, NGAL at 30 ng/mL predicted worsening renal disease (P = .04; specificity 60%, sensitivity 61%).

Urine MCP1 and NGAL changed as subsequent renal disease changed (MCP1, P = .015; NGAL, P = .038), while standard biomarkers (erythrocyte sedimentation rate, anti-double stranded DNA, urine albumin to creatinine ratio, creatinine, complement 3, complement 4, and lymphocytes) did not predict disease activity changes. MCP1 and C3 were seen in a multivariate analysis as independent variables (P less than .001) for active renal disease (Lupus 2013;22 [Suppl.]:O13).

The fact that MCP1 and NGAL are so specific, Dr. Watson said, "may be because they’re expressed directly from the kidney cells. Perhaps we need to begin to validate some of these and move them towards commercialization so we can look towards earlier intervention and monitoring to try and improve the outcome in our patients."

New disease criteria perform better than old

In a separate talk at the congress (Lupus 2013;22[Suppl.]:O12), Dr. Marìa M. Katsicas of the Hospital de Pediatría Prof. Dr. Juan P. Garrahan, in Buenos Aires, presented results from a study comparing the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE, published last year (Arthritis Rheum. 2012;64:2677-86), with the revised American College of Rheumatology criteria for SLE (Arthritis Rheum. 1997;40:1725) in a cohort of juvenile patients.

"The ACR criteria have not been completely evaluated in pediatric patients," Dr. Katsicas explained. "Only one publication describes sensitivity and specificity in Brazilian children" (Clin. Exp. Rheumatol. 1994;12:83-7).

For Dr. Katsicas and her colleagues’ study, experienced pediatric rheumatologists reviewed medical records and prospective data for 107 patients with juvenile-onset SLE, and 124 controls with juvenile idiopathic arthritis, juvenile dermatomyositis, autoimmune hepatitis, juvenile systemic sclerosis, ANCA-associated vasculitis, or Henoch-Schönlein purpura.

Using the SLICC SLE criteria, all of the SLE cases were correctly identified, while under the ACR 1997 criteria, six cases were missed. Sensitivity for the new criteria was 100%, compared with 86% for the ACR criteria, while specificity was 98% and 96% respectively. "It is very important to note that six patients were correctly identified by SLICC and not ACR," Dr. Katsicas said.

Many patients develop hippocampal atrophy

Dr. Simone Appenzeller of the State University of Campinas, São Paulo, Brazil, and her colleagues reported finding MRI evidence of hippocampal atrophy (in one or both lobes) in 24 of 40 juvenile SLE patients, compared with only 1 of 40 controls.

"Studies have suggested that in the hippocampus, which is the brain area important to memory and learning, [there] may be a specific target for some autoantibodies in neuropsychiatric SLE," Dr. Appenzeller told the congress.

"We have previously shown in adults that there is hippocampal atrophy associated with the total dose of corticosteroids," Dr. Appenzeller said (Ann. Rheum. Dis. 2006;65:1585-9), noting that the association was found once again in the current study (P = .019). Atrophy was also associated with anticardiolipin antibodies (P = .009), vasculitis (P = .042), disease duration (P = .001), cognitive impairment (P = .005), age of disease onset (P = .008) and current age (P = .013). However, disease activity and damage scores were not associated with hippocampal atrophy.

Patients that may have hippocampal atrophy should be followed more closely with MRI and cognitive evaluation, Dr. Appenzeller advised, adding that the findings "could allow us to develop strategies to prevent its occurrence" (Lupus 2013;22[Suppl.]:O15)

Neither Dr. Katsicas nor Dr. Appenzeller reported conflicts of interest. Dr. Watson disclosed that Abbott Laboratories provided the NGAL assay for her group’s study at no cost.

BUENOS AIRES – A group of new studies on juvenile-onset systemic lupus erythematosus suggests that investigators are gaining a foothold on noninvasively monitoring renal disease, making more accurate diagnoses, and determining the prevalence of hippocampal atrophy in adolescents with the condition.

One of the three reports presented at the international congress on systemic lupus erythematosus (SLE) involved research from U.K. investigators on novel noninvasive biomarkers that can predict the course of renal disease in juvenile SLE, potentially allowing for earlier intervention, fewer kidney biopsies, and more accurate drug titration.

Researchers from Argentina revealed that new classification criteria for SLE, published in 2012, were more sensitive and specific in juvenile lupus patients than the widely used American College of Rheumatology criteria, which were last revised in 1997.

A third report from Brazil-based investigators found that atrophy of the hippocampus, the part of the brain associated with memory and learning, occurred in nearly two-thirds of a cohort of juvenile SLE patients.

Urine biomarkers for lupus nephritis

Dr. Louise Watson of Alder Hey Children’s NHS Hospital, Liverpool, England, presented findings on novel urine biomarkers from a multicenter, prospective cohort study of 64 SLE patients aged 16 years and younger. "We were keen to look for better ways to monitor the disease through biomarkers, and to move from a more reactive to a more proactive approach," Dr. Watson said at the meeting.

Rather than wait until the onset of proteinuria to start treatment, reliable noninvasive biomarkers "could allow disease to be detected at a much earlier time point, and hopefully help us try and prevent some of the irreversible kidney damage that we might see" associated with juvenile-onset SLE.

Dr. Watson and her colleagues looked at both standard and novel biomarkers in the cohort, and found that two novel ones – monocyte chemoattractant protein 1 (MCP1) and neutrophil gelatinase associated lipocalin (NGAL) – predicted changes in the course of renal disease over a 2-year period. MCP1 was highly predictive of disease improvement, and NGAL of disease progression.

MCP1 at a concentration of 343 pg/mL was a significant predictor of improvement in renal disease (P = .013; specificity 71%, sensitivity 70%), the researchers found. Meanwhile, NGAL at 30 ng/mL predicted worsening renal disease (P = .04; specificity 60%, sensitivity 61%).

Urine MCP1 and NGAL changed as subsequent renal disease changed (MCP1, P = .015; NGAL, P = .038), while standard biomarkers (erythrocyte sedimentation rate, anti-double stranded DNA, urine albumin to creatinine ratio, creatinine, complement 3, complement 4, and lymphocytes) did not predict disease activity changes. MCP1 and C3 were seen in a multivariate analysis as independent variables (P less than .001) for active renal disease (Lupus 2013;22 [Suppl.]:O13).

The fact that MCP1 and NGAL are so specific, Dr. Watson said, "may be because they’re expressed directly from the kidney cells. Perhaps we need to begin to validate some of these and move them towards commercialization so we can look towards earlier intervention and monitoring to try and improve the outcome in our patients."

New disease criteria perform better than old

In a separate talk at the congress (Lupus 2013;22[Suppl.]:O12), Dr. Marìa M. Katsicas of the Hospital de Pediatría Prof. Dr. Juan P. Garrahan, in Buenos Aires, presented results from a study comparing the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE, published last year (Arthritis Rheum. 2012;64:2677-86), with the revised American College of Rheumatology criteria for SLE (Arthritis Rheum. 1997;40:1725) in a cohort of juvenile patients.

"The ACR criteria have not been completely evaluated in pediatric patients," Dr. Katsicas explained. "Only one publication describes sensitivity and specificity in Brazilian children" (Clin. Exp. Rheumatol. 1994;12:83-7).

For Dr. Katsicas and her colleagues’ study, experienced pediatric rheumatologists reviewed medical records and prospective data for 107 patients with juvenile-onset SLE, and 124 controls with juvenile idiopathic arthritis, juvenile dermatomyositis, autoimmune hepatitis, juvenile systemic sclerosis, ANCA-associated vasculitis, or Henoch-Schönlein purpura.

Using the SLICC SLE criteria, all of the SLE cases were correctly identified, while under the ACR 1997 criteria, six cases were missed. Sensitivity for the new criteria was 100%, compared with 86% for the ACR criteria, while specificity was 98% and 96% respectively. "It is very important to note that six patients were correctly identified by SLICC and not ACR," Dr. Katsicas said.

Many patients develop hippocampal atrophy

Dr. Simone Appenzeller of the State University of Campinas, São Paulo, Brazil, and her colleagues reported finding MRI evidence of hippocampal atrophy (in one or both lobes) in 24 of 40 juvenile SLE patients, compared with only 1 of 40 controls.

"Studies have suggested that in the hippocampus, which is the brain area important to memory and learning, [there] may be a specific target for some autoantibodies in neuropsychiatric SLE," Dr. Appenzeller told the congress.

"We have previously shown in adults that there is hippocampal atrophy associated with the total dose of corticosteroids," Dr. Appenzeller said (Ann. Rheum. Dis. 2006;65:1585-9), noting that the association was found once again in the current study (P = .019). Atrophy was also associated with anticardiolipin antibodies (P = .009), vasculitis (P = .042), disease duration (P = .001), cognitive impairment (P = .005), age of disease onset (P = .008) and current age (P = .013). However, disease activity and damage scores were not associated with hippocampal atrophy.

Patients that may have hippocampal atrophy should be followed more closely with MRI and cognitive evaluation, Dr. Appenzeller advised, adding that the findings "could allow us to develop strategies to prevent its occurrence" (Lupus 2013;22[Suppl.]:O15)

Neither Dr. Katsicas nor Dr. Appenzeller reported conflicts of interest. Dr. Watson disclosed that Abbott Laboratories provided the NGAL assay for her group’s study at no cost.

BUENOS AIRES – A group of new studies on juvenile-onset systemic lupus erythematosus suggests that investigators are gaining a foothold on noninvasively monitoring renal disease, making more accurate diagnoses, and determining the prevalence of hippocampal atrophy in adolescents with the condition.

One of the three reports presented at the international congress on systemic lupus erythematosus (SLE) involved research from U.K. investigators on novel noninvasive biomarkers that can predict the course of renal disease in juvenile SLE, potentially allowing for earlier intervention, fewer kidney biopsies, and more accurate drug titration.

Researchers from Argentina revealed that new classification criteria for SLE, published in 2012, were more sensitive and specific in juvenile lupus patients than the widely used American College of Rheumatology criteria, which were last revised in 1997.

A third report from Brazil-based investigators found that atrophy of the hippocampus, the part of the brain associated with memory and learning, occurred in nearly two-thirds of a cohort of juvenile SLE patients.

Urine biomarkers for lupus nephritis

Dr. Louise Watson of Alder Hey Children’s NHS Hospital, Liverpool, England, presented findings on novel urine biomarkers from a multicenter, prospective cohort study of 64 SLE patients aged 16 years and younger. "We were keen to look for better ways to monitor the disease through biomarkers, and to move from a more reactive to a more proactive approach," Dr. Watson said at the meeting.

Rather than wait until the onset of proteinuria to start treatment, reliable noninvasive biomarkers "could allow disease to be detected at a much earlier time point, and hopefully help us try and prevent some of the irreversible kidney damage that we might see" associated with juvenile-onset SLE.

Dr. Watson and her colleagues looked at both standard and novel biomarkers in the cohort, and found that two novel ones – monocyte chemoattractant protein 1 (MCP1) and neutrophil gelatinase associated lipocalin (NGAL) – predicted changes in the course of renal disease over a 2-year period. MCP1 was highly predictive of disease improvement, and NGAL of disease progression.

MCP1 at a concentration of 343 pg/mL was a significant predictor of improvement in renal disease (P = .013; specificity 71%, sensitivity 70%), the researchers found. Meanwhile, NGAL at 30 ng/mL predicted worsening renal disease (P = .04; specificity 60%, sensitivity 61%).

Urine MCP1 and NGAL changed as subsequent renal disease changed (MCP1, P = .015; NGAL, P = .038), while standard biomarkers (erythrocyte sedimentation rate, anti-double stranded DNA, urine albumin to creatinine ratio, creatinine, complement 3, complement 4, and lymphocytes) did not predict disease activity changes. MCP1 and C3 were seen in a multivariate analysis as independent variables (P less than .001) for active renal disease (Lupus 2013;22 [Suppl.]:O13).

The fact that MCP1 and NGAL are so specific, Dr. Watson said, "may be because they’re expressed directly from the kidney cells. Perhaps we need to begin to validate some of these and move them towards commercialization so we can look towards earlier intervention and monitoring to try and improve the outcome in our patients."

New disease criteria perform better than old

In a separate talk at the congress (Lupus 2013;22[Suppl.]:O12), Dr. Marìa M. Katsicas of the Hospital de Pediatría Prof. Dr. Juan P. Garrahan, in Buenos Aires, presented results from a study comparing the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE, published last year (Arthritis Rheum. 2012;64:2677-86), with the revised American College of Rheumatology criteria for SLE (Arthritis Rheum. 1997;40:1725) in a cohort of juvenile patients.

"The ACR criteria have not been completely evaluated in pediatric patients," Dr. Katsicas explained. "Only one publication describes sensitivity and specificity in Brazilian children" (Clin. Exp. Rheumatol. 1994;12:83-7).

For Dr. Katsicas and her colleagues’ study, experienced pediatric rheumatologists reviewed medical records and prospective data for 107 patients with juvenile-onset SLE, and 124 controls with juvenile idiopathic arthritis, juvenile dermatomyositis, autoimmune hepatitis, juvenile systemic sclerosis, ANCA-associated vasculitis, or Henoch-Schönlein purpura.

Using the SLICC SLE criteria, all of the SLE cases were correctly identified, while under the ACR 1997 criteria, six cases were missed. Sensitivity for the new criteria was 100%, compared with 86% for the ACR criteria, while specificity was 98% and 96% respectively. "It is very important to note that six patients were correctly identified by SLICC and not ACR," Dr. Katsicas said.

Many patients develop hippocampal atrophy

Dr. Simone Appenzeller of the State University of Campinas, São Paulo, Brazil, and her colleagues reported finding MRI evidence of hippocampal atrophy (in one or both lobes) in 24 of 40 juvenile SLE patients, compared with only 1 of 40 controls.

"Studies have suggested that in the hippocampus, which is the brain area important to memory and learning, [there] may be a specific target for some autoantibodies in neuropsychiatric SLE," Dr. Appenzeller told the congress.

"We have previously shown in adults that there is hippocampal atrophy associated with the total dose of corticosteroids," Dr. Appenzeller said (Ann. Rheum. Dis. 2006;65:1585-9), noting that the association was found once again in the current study (P = .019). Atrophy was also associated with anticardiolipin antibodies (P = .009), vasculitis (P = .042), disease duration (P = .001), cognitive impairment (P = .005), age of disease onset (P = .008) and current age (P = .013). However, disease activity and damage scores were not associated with hippocampal atrophy.

Patients that may have hippocampal atrophy should be followed more closely with MRI and cognitive evaluation, Dr. Appenzeller advised, adding that the findings "could allow us to develop strategies to prevent its occurrence" (Lupus 2013;22[Suppl.]:O15)

Neither Dr. Katsicas nor Dr. Appenzeller reported conflicts of interest. Dr. Watson disclosed that Abbott Laboratories provided the NGAL assay for her group’s study at no cost.