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Observational Study
. 2022 Apr;107(4):371-376.
doi: 10.1136/archdischild-2021-322114. Epub 2021 Oct 22.

M-ficolin: a valuable biomarker to identify leukaemia from juvenile idiopathic arthritis

Ninna Brix  1   2 , Mia Glerup  3 , Steffen Thiel  4 , Clara Elbæk Mistegaard  4   5 , Regitze Gyldenholm Skals  6 , Lillemor Berntson  7 , Anders Fasth  8 , Susan Mary Nielsen  9 , Ellen Nordal  10   11 , Marite Rygg  12   13 , Henrik Hasle  14 , Birgitte Klug Albertsen  14 , Troels Herlin  14 ; Nordic Study Group of Pediatric Rheumatology (NoSPeR) group
Affiliations
Observational Study

M-ficolin: a valuable biomarker to identify leukaemia from juvenile idiopathic arthritis

Ninna Brix et al. Arch Dis Child. 2022 Apr.

Abstract

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.

Keywords: cell biology; pain; rheumatology; statistics.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Flow chart of the study population. ALL, acute lymphoblastic leukaemia; JIA, juvenile idiopathic arthritis.
Figure 2
Figure 2
Box plots illustrating for the concentration of CL-K1, M-ficolin and MASP-3 in all (n=151), ALLarthropathy (n=27) and JIA (n=238) at baseline and in all in a paired cohort (n=73) at baseline, 29 days and 6 months of follow-up. ALLarthropathy, acute lymphoblastic leukaemia presenting with arthropathy; JIA, juvenile idiopathic arthritis.
Figure 3
Figure 3
Receiver operating characteristics curves with optimal cut-offs for non-optimism corrected models. CRP, C-reactive protein.
See this image and copyright information in PMC

References

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