TY - JOUR
T1 - M-ficolin
T2 - a valuable biomarker to identify leukaemia from juvenile idiopathic arthritis
AU - Brix, Ninna
AU - Glerup, Mia
AU - Thiel, Steffen
AU - Mistegaard, Clara Elbæk
AU - Skals, Regitze Gyldenholm
AU - Berntson, Lillemor
AU - Fasth, Anders
AU - Nielsen, Susan Mary
AU - Nordal, Ellen
AU - Rygg, Marite
AU - Hasle, Henrik
AU - Albertsen, Birgitte Klug
AU - Herlin, Troels
AU - Nordic Study Group of Pediatric Rheumatology (NoSPeR) group
N1 - © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2022/3/17
Y1 - 2022/3/17
N2 - OBJECTIVE: Distinction on clinical grounds between acute lymphoblastic leukaemia presenting with arthropathy (ALLarthropathy) and juvenile idiopathic arthritis (JIA) is difficult, as the clinical and paraclinical signs of leukaemia may be vague. The primary aim was to examine the use of lectin complement pathway proteins as markers to differentiate ALLarthropathy from JIA. The secondary aims were to compare the protein levels at baseline and follow-up in a paired number of children with ALL and to examine the correlation with haematology counts, erythrocyte sedimentation reaction (ESR), C-reactive protein (CRP), blasts, relapse and death.STUDY DESIGN: In this observational study, we measured M-ficolin, CL-K1 and MASP-3 in serum from children with ALL (n=151) and JIA (n=238) by time-resolved immunofluorometric assays. Logistic regression was used for predictions of ALL risk, considering the markers as the respective exposures. We performed internal validation using repeated '10-fold cross-validation' with 100 repetitions computing the area under the curve (AUC) as well as positive and negative predictive values in order to evaluate the predictive performance.RESULTS: The level of M-ficolin was higher in JIA than ALLtotal and the ALLarthropathy subgroup. The M-ficolin level normalised after remission of ALL. M-ficolin could differentiate ALL from JIA with an AUC of 94% and positive predictive value (PPV) of 95%, exceeding CRP and haemoglobin. In a dichotomised predictive model with optimal cut-offs for M-ficolin, platelets and haemoglobin, AUC was 99% and PPV 98% in detecting ALL from JIA.CONCLUSION: M-ficolin is a valuable marker to differentiate the child with ALL from JIA.
AB - OBJECTIVE: Distinction on clinical grounds between acute lymphoblastic leukaemia presenting with arthropathy (ALLarthropathy) and juvenile idiopathic arthritis (JIA) is difficult, as the clinical and paraclinical signs of leukaemia may be vague. The primary aim was to examine the use of lectin complement pathway proteins as markers to differentiate ALLarthropathy from JIA. The secondary aims were to compare the protein levels at baseline and follow-up in a paired number of children with ALL and to examine the correlation with haematology counts, erythrocyte sedimentation reaction (ESR), C-reactive protein (CRP), blasts, relapse and death.STUDY DESIGN: In this observational study, we measured M-ficolin, CL-K1 and MASP-3 in serum from children with ALL (n=151) and JIA (n=238) by time-resolved immunofluorometric assays. Logistic regression was used for predictions of ALL risk, considering the markers as the respective exposures. We performed internal validation using repeated '10-fold cross-validation' with 100 repetitions computing the area under the curve (AUC) as well as positive and negative predictive values in order to evaluate the predictive performance.RESULTS: The level of M-ficolin was higher in JIA than ALLtotal and the ALLarthropathy subgroup. The M-ficolin level normalised after remission of ALL. M-ficolin could differentiate ALL from JIA with an AUC of 94% and positive predictive value (PPV) of 95%, exceeding CRP and haemoglobin. In a dichotomised predictive model with optimal cut-offs for M-ficolin, platelets and haemoglobin, AUC was 99% and PPV 98% in detecting ALL from JIA.CONCLUSION: M-ficolin is a valuable marker to differentiate the child with ALL from JIA.
KW - cell biology
KW - pain
KW - rheumatology
KW - statistics
UR - http://www.scopus.com/inward/record.url?scp=85127729190&partnerID=8YFLogxK
U2 - 10.1136/archdischild-2021-322114
DO - 10.1136/archdischild-2021-322114
M3 - Journal article
C2 - 34686494
SN - 0003-9888
VL - 107
SP - 371
EP - 376
JO - Archives of Disease in Childhood
JF - Archives of Disease in Childhood
IS - 4
ER -