Haptoglobin in Juvenile Idiopathic Arthritis

Abstract Background Haptoglobin (Hp), a liver derived acute phase inflammatory protein (APP), has scarcely been studied in juvenile idiopathic arthritis (JIA). Hp can occur in blood as two isoforms (Hp1 and Hp2) in precursor and mature forms. Routine clinical chemistry immunoturbidimetry does not di...

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Main Authors: Lillemor Berntson, Jakob Palm, Fredrik Axling, Peter Zarelius, Per M. Hellström, Dominic-Luc Webb
Format: Article
Language:English
Published: BMC 2022-12-01
Series:Pediatric Rheumatology Online Journal
Subjects:
Online Access:https://doi.org/10.1186/s12969-022-00777-5
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author Lillemor Berntson
Jakob Palm
Fredrik Axling
Peter Zarelius
Per M. Hellström
Dominic-Luc Webb
author_facet Lillemor Berntson
Jakob Palm
Fredrik Axling
Peter Zarelius
Per M. Hellström
Dominic-Luc Webb
author_sort Lillemor Berntson
collection DOAJ
description Abstract Background Haptoglobin (Hp), a liver derived acute phase inflammatory protein (APP), has scarcely been studied in juvenile idiopathic arthritis (JIA). Hp can occur in blood as two isoforms (Hp1 and Hp2) in precursor and mature forms. Routine clinical chemistry immunoturbidimetry does not discern these forms. It is unknown how different forms relate to disease activity in JIA. Our aims were to determine allele frequency and plasma concentrations of different Hp forms at higher versus lower JIA disease activity and compare to other APPs. Methods Plasma from JIA (n = 77) and healthy (n = 42) children were analyzed for apparent Hp allelic frequency and densitometric concentrations of alpha forms by Western blot (WB). Polymerase chain reaction (PCR) (buffy coat) was performed in a subset to estimate conformity with genetics. At higher versus lower juvenile arthritis disease activity score (JADAS27) (which includes erythrocyte sedimentation rate (ESR)), total mature Hp concentration from WB was compared and correlated against immunoturbidimetry and total protein, albumin, serum amyloid A (SAA) and C-reactive protein (CRP). Results At 300-fold dilution needed to study mature forms in Western blot, precursors were undetectable. Hp2 contributed most signal in most samples. Hp allele frequency was similar in JIA and controls. Both mature forms, taken separately or by sum, declined following treatment, but remained above concentrations of healthy controls, even in a remission subset that achieved JADAS27 < 1. Densitometry correlated with immunoturbidimetry. Hp concentrations correlated with JADAS27, albumin (negatively), CRP and SAA with immunoturbidimetric method correlating strongest to JADAS27 (Spearman R ~ 0.6, p < 0.0001). Conclusion Hp allele frequency in JIA is similar to the general population, indicating that children with JIA should have the same possibility as in healthy children to produce preHp2 (zonulin), thought to increase intestinal permeability. Circulating Hp concentrations largely parallel other APPs and ESR; none of these measures correlate very strongly to JADAS27 score but Hp can be measured from capillary sampling which is impossible with ESR.
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spelling doaj.art-30618e0de1264109853c4f85782ca8bc2022-12-22T04:23:38ZengBMCPediatric Rheumatology Online Journal1546-00962022-12-0120111010.1186/s12969-022-00777-5Haptoglobin in Juvenile Idiopathic ArthritisLillemor Berntson0Jakob Palm1Fredrik Axling2Peter Zarelius3Per M. Hellström4Dominic-Luc Webb5Department of Women’s and Children’s Health, Uppsala UniversityGastroenterology and Hepatology Unit, Department of Medical Sciences, Uppsala UniversityDepartment of Surgical Sciences, Uppsala UniversityGastroenterology and Hepatology Unit, Department of Medical Sciences, Uppsala UniversityGastroenterology and Hepatology Unit, Department of Medical Sciences, Uppsala UniversityGastroenterology and Hepatology Unit, Department of Medical Sciences, Uppsala UniversityAbstract Background Haptoglobin (Hp), a liver derived acute phase inflammatory protein (APP), has scarcely been studied in juvenile idiopathic arthritis (JIA). Hp can occur in blood as two isoforms (Hp1 and Hp2) in precursor and mature forms. Routine clinical chemistry immunoturbidimetry does not discern these forms. It is unknown how different forms relate to disease activity in JIA. Our aims were to determine allele frequency and plasma concentrations of different Hp forms at higher versus lower JIA disease activity and compare to other APPs. Methods Plasma from JIA (n = 77) and healthy (n = 42) children were analyzed for apparent Hp allelic frequency and densitometric concentrations of alpha forms by Western blot (WB). Polymerase chain reaction (PCR) (buffy coat) was performed in a subset to estimate conformity with genetics. At higher versus lower juvenile arthritis disease activity score (JADAS27) (which includes erythrocyte sedimentation rate (ESR)), total mature Hp concentration from WB was compared and correlated against immunoturbidimetry and total protein, albumin, serum amyloid A (SAA) and C-reactive protein (CRP). Results At 300-fold dilution needed to study mature forms in Western blot, precursors were undetectable. Hp2 contributed most signal in most samples. Hp allele frequency was similar in JIA and controls. Both mature forms, taken separately or by sum, declined following treatment, but remained above concentrations of healthy controls, even in a remission subset that achieved JADAS27 < 1. Densitometry correlated with immunoturbidimetry. Hp concentrations correlated with JADAS27, albumin (negatively), CRP and SAA with immunoturbidimetric method correlating strongest to JADAS27 (Spearman R ~ 0.6, p < 0.0001). Conclusion Hp allele frequency in JIA is similar to the general population, indicating that children with JIA should have the same possibility as in healthy children to produce preHp2 (zonulin), thought to increase intestinal permeability. Circulating Hp concentrations largely parallel other APPs and ESR; none of these measures correlate very strongly to JADAS27 score but Hp can be measured from capillary sampling which is impossible with ESR.https://doi.org/10.1186/s12969-022-00777-5Arthritis juvenileAcute phase proteinsHaptoglobinBiomarkers
spellingShingle Lillemor Berntson
Jakob Palm
Fredrik Axling
Peter Zarelius
Per M. Hellström
Dominic-Luc Webb
Haptoglobin in Juvenile Idiopathic Arthritis
Pediatric Rheumatology Online Journal
Arthritis juvenile
Acute phase proteins
Haptoglobin
Biomarkers
title Haptoglobin in Juvenile Idiopathic Arthritis
title_full Haptoglobin in Juvenile Idiopathic Arthritis
title_fullStr Haptoglobin in Juvenile Idiopathic Arthritis
title_full_unstemmed Haptoglobin in Juvenile Idiopathic Arthritis
title_short Haptoglobin in Juvenile Idiopathic Arthritis
title_sort haptoglobin in juvenile idiopathic arthritis
topic Arthritis juvenile
Acute phase proteins
Haptoglobin
Biomarkers
url https://doi.org/10.1186/s12969-022-00777-5
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