Laboratory workup supporting common rheumatology diagnoses

Affiliation: 

1. George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mureș
2. Pediatrics Clinic I, Emergency Clinical County Hospital Târgu-Mureș

In rheumatologic diseases, the diagnosis is mostly established through patient history and complete physical examination, while laboratory tests serve to support or rule out the diagnosis (1,2). Additionally, lab tests allow for general evaluation, identification of inflammation, and monitoring of disease progression and treatment side effects.

Laboratory tests for assessing patients with rheumatologic conditions include routine analyses: complete blood count (CBC), peripheral smear, common inflammatory markers – C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), urinalysis, transaminases, creatinine, urea, lactate dehydrogenase  (LDH)– followed by specific tests based on the history and clinical signs justifying their use (3).

The recommendation to perform and interpret a lab test must be made in the clinical context. For example, ordering tests such as antinuclear antibodies (ANA) or anti-DNA antibodies is not advised in a patient presenting only with arthralgia, without inflammatory signs. The presence of certain antibodies, such as ANA or anti-neutrophil cytoplasmic autoantibodies (ANCA), does not necessarily mean the patient has a rheumatologic disease (4).

Referral to pediatric rheumatology services for positive rheumatologic lab tests in patients without significant clinical complaints is not justified. Not all patients with a positive rheumatoid factor have juvenile idiopathic arthritis (JIA), and not all patients with a positive ANA have systemic lupus erythematosus (SLE).

Considering the shortage of pediatric rheumatologists, initial evaluation may be performed by a general practitioner or pediatrician before referral to pediatric rheumatology. Laboratory testing for suspected rheumatologic conditions should begin when the patient shows inflammatory signs or persistent fever, weight loss, night sweats, lymphadenopathy, fatigue, bone pain waking the child at night, or mismatch between history and clinical findings.

ANA tests are most commonly ordered for children referred to pediatric rheumatologists. However, 70–90% of these children are not diagnosed with rheumatologic diseases at the initial visit, and symptoms often resolve over time (5). Overuse of ANA testing can cause anxiety, unnecessary investigations, and inappropriate treatments (2).

ANA testing should be ordered only when there is clinical suspicion of SLE. Clinical signs raising suspicion include joint symptoms (arthritis in at least two joints), neurologic involvement (seizures, psychosis, delirium), serositis (pleuritis, pericarditis, ascites), mucocutaneous signs (malar rash, alopecia, oral ulcers), and fever (5,6). It is also indicated when lab tests show anemia, thrombocytopenia, hematuria, proteinuria, hypoalbuminemia, or low complement levels (C4, C3), after ruling out other conditions.

According to 2019 The European Alliance of Associations for Rheumatology (EULAR) criteria, the diagnosis of SLE requires at least a positive ANA at a titer ≥1:80. Rarely, 1–2% of patients may have SLE without ANA positivity due to antigen absence in the test substrate or early complement deficiency (C2, C4). In cases of severe proteinuria, ANA may initially be negative and become positive after treatment. Once the diagnosis of lupus is established, repeated ANA titers are not useful for disease monitoring (7,8).

A positive ANA result does not necessarily mean SLE, as positive titers can also be found in healthy individuals, often among family members of those with autoimmune connective tissue diseases (9).

ANA may also be positive in conditions like JIA, scleroderma, dermatomyositis, antiphospholipid syndrome, Sjögren’s syndrome, Raynaud’s syndrome, mixed connective tissue disease, autoimmune hepatitis, primary biliary cirrhosis, ulcerative colitis, autoimmune thyroiditis, lymphoma, leukemia, solid tumors, immune thrombocytopenic purpura, autoimmune hemolytic anemia, diabetes mellitus, hyperthyroidism, chronic Epstein-Barr virus infection, hepatitis C virus, endocarditis, tuberculosis, HIV. ANA positivity is also found in 2–15% of healthy children (1,10,11). Retesting ANA is not recommended unless new clinical signs appear (12).

In cases of very high ANA titers (e.g., >1:640) without other symptoms or an established diagnosis, close follow-up is recommended (8). In initially asymptomatic individuals with autoantibodies, autoimmune diseases may develop over time. This subclinical phase is considered an early stage of autoimmune disease (13).

ANA can be tested using ELISA, but the gold standard is immunofluorescence. If ELISA is negative but autoimmune disease is suspected, immunofluorescence should be used. If ANA is positive, the fluorescence pattern (diffuse, peripheral, speckled, nucleolar, centromere) is reported, and specific antibodies are tested to guide diagnosis.

• Anti-U1 RNP antibodies: associated with SLE, systemic sclerosis, MCTD
• Anti-Sm antibodies: highly specific for SLE, remain positive during remission
• Anti-SS-A (Ro): associated with SLE, primary Sjögren’s (70%), neonatal lupus, subacute cutaneous lupus, secondary Sjögren’s, undifferentiated connective tissue disease
• Anti-Ro52 antibodies: found in SLE, neonatal lupus, Sjögren’s syndrome, myositis, scleroderma
• Anti-SCL-70 antibodies: associated with systemic sclerosis
• Anti-PM-SCL antibodies: overlap syndromes (scleroderma + polymyositis/dermatomyositis)
• Anti-Jo1 antibodies: dermatomyositis, polymyositis
• Anti-centromere antibodies: CREST syndrome, diffuse scleroderma
• Anti-PCNA antibodies: SLE
• Anti-dsDNA antibodies: very specific for SLE; used for disease monitoring
• Anti-nucleosome antibodies: seen in SLE
• Anti-histone antibodies: drug-induced lupus, SLE, rheumatoid arthritis (RA)
• Anti-ribosomal P antibodies: SLE with neurologic involvement
• Anti-AMA-M2 antibodies: primary biliary cirrhosis
• Anti-DFS70 antibodies: not associated with systemic autoimmune disease—presence may exclude such conditions (7,8,14)

Anti-dsDNA antibodies are among SLE diagnostic criteria, with high specificity, though their absence doesn’t rule out SLE (15). Testing is recommended when ANA is positive and there’s clinical suspicion of lupus. Routine testing for arthralgia alone is not recommended. High titers may indicate impending flare or lupus nephritis (1,16).

Anti-dsDNA positivity may also occur in autoimmune hepatitis, viral hepatitis, mononucleosis, familial Mediterranean fever, lymphoma, primary biliary cirrhosis, drug-induced lupus (e.g., penicillin, hydralazine, etanercept, infliximab), Sjögren’s syndrome, sarcoidosis, systemic sclerosis, antiphospholipid syndrome, JIA, or even healthy individuals (especially those with lupus relatives) (17).

ANA testing is not necessary to diagnose JIA, but its presence is a poor prognostic factor and increases uveitis risk. Ophthalmologic screening is mandatory in JIA patients (5). ANA positivity in young girls with early-onset JIA, few affected joints, asymmetric joint involvement, and no hip involvement may indicate a distinct JIA subgroup (18).

ANA positivity in a child with Raynaud’s phenomenon suggests higher risk of developing mixed connective tissue disease (MCTD) or scleroderma (5).

In conclusion, ANA testing should be performed only when there’s a strong suspicion of SLE, MCTD, JIA, Juvenile dermatomyositis, systemic sclerosis, or Sjögren’s syndrome—not as a screening method (19).

Another common reason for pediatric rheumatology referral is a positive rheumatoid factor (RF), often ordered for arthralgia.

In pediatric patients, RF should be tested only when JIA with polyarticular onset is suspected. Polyarticular forms are divided based on RF status (positive: two positive tests 3 months apart; or negative). RF positivity is a poor prognostic factor, associated with joint erosions, longer disease duration, symmetric involvement of large/small joints, subcutaneous nodules, and need for aggressive treatment (1,4,20,21).

RF is nonspecific. Patients with infections — Cytomegalovirus, Epstein Barr Virus, tuberculosis, Hepatitis B, C, Treponema pallidum, endocarditis, lymphoma, primary biliary cirrhosis, JIA, SLE, sarcoidosis, scleroderma, Sjögren’s syndrome, mixed connective tissue disease, cryoglobulinemia, dermatomyositis — or smokers may have a positive rheumatoid factor, as well as 2–7% of healthy young individuals (4, 8, 21).

Retesting children with JIA who are initially RF negative is unnecessary, as they rarely later convert to RF positive (16).

Since RF lacks high specificity, a more specific test was sought, leading to the identification of anti-cyclic citrullinated peptide antibodies (anti-CCP) (21).

Anti-CCP antibodies should be requested when the patient is diagnosed with polyarticular JIA and is RF-positive, as this test is almost exclusively positive in this form (1, 4, 20). In both RA and JIA, the presence of anti-CCP antibodies is associated with more erosive joint disease and is even a better predictor of this than RF (8).

Low anti-CCP titers can also be found in other JIA forms, such as RF-negative polyarticular JIA, but also in SLE, ankylosing spondylitis, scleroderma, and chronic hepatitis C (1, 15, 22).

In adults presenting only with arthralgia, a positive anti-CCP test predicts the development of RA in 90% of cases within 3 years (21). Identifying these antibodies at JIA onset indicates the need for more aggressive treatment (16).

Routine pediatric evaluations often include the  Antistreptolysin O test (ASO). When positive, family physicians or pediatricians—sometimes under parental pressure—refer the child to a pediatric rheumatologist. Other streptococcal infection markers include anti hyaluronidase, anti deoxyribonuclease B (ADB), and antistreptokinase antibodies.

An elevated ASO without clinical signs of rheumatic fever (according to Jones criteria) should be interpreted as a post-streptococcal state. ASO rises within a week after infection, peaks in 3–6 weeks, and returns to normal in 6–12 months if no reinfection occurs. ASO is also elevated in post-streptococcal reactive arthritis. ADB peaks in 6–8 weeks and decreases in 3 months (18).

Group A beta-hemolytic Streptococcus is one of the etiologic agents of IgA vasculitis, hence throat swabs and ASO titers are needed for diagnosis. A positive ASLO but a negative throat swab does not justify antibiotic treatment.

False-positive ASO results can occur in tuberculosis, active viral hepatitis, bacterial contamination, presence of Bacillus cereus or Pseudomonas in serum, or lipemic serum (23).

Routine HLA-B27 testing for nonspecific low back pain often leads to false positives and misdiagnosis. It should only be requested in cases of inflammatory back pain: insidious onset, prolonged morning stiffness, nighttime pain, worsening with rest and improving with activity, alternating buttock pain, good response to nonsteroidal anti-inflammatory drugs (NSAIDs), or in the presence of enthesitis, sacroiliitis, acute symptomatic uveitis, recent gastrointestinal or genitourinary infection, or family history of ankylosing spondylitis, enthesitis-related arthritis, Reiter’s syndrome, or inflammatory bowel disease (24,25).

HLA-B27 is a diagnostic criterion for enthesitis-related arthritis (ERA), being present in 65–80% of cases. Boys over age 6 with JIA should be tested. It may also be found in 5–10% of the healthy population (20).

Macrophage Activation Syndrome (MAS) is a pediatric rheumatology emergency, involving a major inflammatory reaction with T cell and macrophage activation and high pro-inflammatory cytokine release (20, 26). It’s life-threatening and can cause multi-organ failure, requiring urgent recognition and treatment.

MAS is suspected in systemic JIA patients whose condition worsen despite proper treatment, presenting with persistent fever, cytopenias, neurologic decline, coagulopathies, bleeding, splenomegaly.

Lab signs:

• Early thrombocytopenia
• Extremely high ferritin (20, 27)
• Decreased WBCs and hemoglobin
• Decreased ESR due to fibrinogen consumption, increased CRP (due to IL-6)
• Increased LDH (cell damage), liver dysfunction (elevated alanine aminotransferase, Aspartate aminotransferase, bilirubin, triglycerides), low albumin
• Coagulation disorders: low fibrinogen, increased PT/INR/PTT, D-dimers (26)

Bone marrow may show hemophagocytosis, but absence does not exclude diagnosis and should not delay treatment (27,28).

Ferritin >10,000 ng/mL is highly suggestive of MAS (28,29). Even with normal levels, repeat testing is advised if MAS is suspected. Ferritin correlates with disease activity and treatment response (30,31,32).

Other MAS markers: low (Natural Killer) NK cell activity, CD25 (T cell activation), CD163 (macrophage activation), IL-18, CXCL9 (IFN-γ bioactivity), though not widely available (26,33).

Diagnostic Criteria of MAS:

• EULAR 2016: Suspected/confirmed JIA + persistent fever + ferritin >684 ng/mL + 2 of:
  • Platelets ≤ 181,000/μL
  • AST > 48 U/L
  • Triglycerides > 156 mg/dL
  • Fibrinogen ≤ 360 mg/dL
• HLH-2004 criteria: ≥5 of: fever, splenomegaly, ≥2 cell lines affected (Hemoglobin < 90 g/L), Platelets <100 x 10⁹/L, Neutrophils <1.0 x 10⁹/L), hypertriglyceridemia/hypofibrinogenemia, hemophagocytosis, low NK activity, ferritin ≥500 μg/L, CD25 >2400 U/mL
• HScore >169 also suggests MAS; includes immunosuppression, hepatosplenomegaly, ferritin >6000 ng/mL without requiring NK/CD25 testing.

MAS can also occur in SLE, Kawasaki disease, juvenile dermatomyositis, recurrent fever syndromes, Multisystem inflammatory syndrome in children (MIS-C) (27,30).

Kidney Involvement is seen in SLE, IgA vasculitis, scleroderma, Sjögren’s syndrome, juvenile dermatomyositis, Kawasaki disease, ANCA vasculitis, amyloidosis.

• Lupus nephritis is more frequent in pediatric-onset SLE. Monitoring: creatinine, urea, urinalysis. Signs: hematuria, proteinuria, red blood cell casts. If proteinuria is present, measure 24-hour proteinuria. Kidney biopsy is essential for confirming diagnosis and disease activity (24, 34–36).
• In systemic/polarticular JIA, kidney monitoring is essential due to risk of amyloidosis (proteinuria ± hematuria).
• Scleroderma renal crisis (rare in children): acute kidney injury, hypertension, microangiopathic hemolytic anemia, thrombocytopenia (37).
• IgA vasculitis: renal issues may occur early or later. Monitoring for 6–12 months post-onset is required—even if initially normal. Older children with severe GI symptoms, necrosis, or persistent purpura are at higher risk (38–40).
• Juvenile dermatomyositis: rare cases of IgA nephropathy, nephrotic syndrome, or rhabdomyolysis-induced kidney injury described (37,41).
• Kawasaki disease: sterile pyuria common; may mimic urinary tract infection. (24).

Inflammatory Markers – provide valuable insights, but should always be interpreted in clinical context. No single marker confirms a diagnosis, but together they help monitor disease activity, assess treatment response, and identify complications. The most commonly used markers include: ESR – a nonspecific marker that increases in most inflammatory conditions, it rises slowly and is useful for detecting chronic inflammation and CRP – increases more rapidly in acute inflammation. 

ESR and CRP are usually high in active disease; in SLE, high CRP may suggest infection or serositis. CRP ↑ + ESR ↓ can indicate MAS in SLE (24).

A newer, promising marker in pediatric rheumatology is Calprotectin: an acute phase protein secreted by activated monocytes and neutrophils (not liver-derived). It’s stable, easy to measure, and useful for detecting subclinical inflammation. Originally used in inflammatory bowel disease, now used in rheumatology. Calprotectin can be measured in blood, saliva, synovial fluid and urine. (42–44).

High calprotectin after stopping nonsteroidal anti-inflammatory drugs, methotrexate, or etanercept can predict relapse (45).

Helpful in early diagnosis and differential diagnosis of systemic JIA, more elevated than in leukemia or infection (46,47).

EULAR/PReS 2024 recommends measuring calprotectin and Interleukin-18 to support sJIA/ Adult Onset Still’s Disease (AOSD) diagnosis (48).

Elevated levels predict joint erosion in JIA, may outperform Interleukin-6 and Tumor necrosis factor (TNF-alpha) (49). Also found in SLE and Kawasaki disease (linked to coronary aneurysms), and in IgA vasculitis (associated with kidney damage severity) (50,51).

Conclusion

Lab tests must be interpreted in the clinical context. Unjustified testing should be avoided. Repeated tests, when appropriate, can help assess patients and even predict disease progression.

1. Colleen K. Correll, MD, MPH, Logan G. Spector,, Lei Zhang, ScM, Bryce A. Binstadt, Richard K. Vehe. Use of rheumatology laboratory studies among primary pediatricians. Clin Pediatr (Phila). 2016 December; 55(14): 1279–1288.
2. Erhan Aygün et al. Antinuclear antibody testing in a Turkish pediatrics clinic: is it always necessary? Pan African Medical Journal. 2019;32:181
3. Austin M. Dalrymple, Terry L. Moore. Laboratory Evaluation in Pediatric Autoimmune Diseases. Pediatr Rev (2015) 36 (11): 496–502.
4. Biman Saikia, Amit Rawat, Pandiarajan Vignesh ^. Autoantibodies and their Judicious Use in Pediatric Rheumatology Practice. Indian J Pediatr. 2016 Jan;83(1):53-62
5. Ostrov BE (2023) Reliability and reproducibility of antinuclear antibody testing in pediatric rheumatology practice. Front. Med. 9:1071115 
6. Aringer et al. 2019 EULAR/ACR Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019 Septembe; 71(9): 1400–1412
7. Sterling G. West, Rheumatology Secrets,2015 Kathryn Hobbs, Chapter 6 Laboratory Evaluation, pg 48-57.
8. Hani Almoallim, Mohamed Cheikh. Skilss in Rheumatology, 2021 Altaf Abdulkhaliq, Manal Alotaibi. Chapter 3 Laboratory Interpretation of Rheumatic Diseases, pg 67-82
9. J-F Wu , Y-H Yang, L-C Wang, J-H Lee, E-Y Shen, B-L Chiang. Clin Exp Rheumatol 2007 Sep-Oct;25(5):782-5. Comparative usefulness of C-reactive protein and erythrocyte sedimentation rate in juvenile rheumatoid arthritis. 
10. Malleson et al. Review for the generalist: The antinuclear antibody test in children – When to use it and what to do with a positive titer. Pediatric Rheumatology 2010, 8:27.
11. M anjari Agarwal & Sujata Sawhney.Laboratory Tests in Pediatric Rheumatology. Indian J Pediatr (2010) 77:1011–1016
12. Yazdany et al. Choosing Wisely: The American College of Rheumatology’s Top 5 List of Things Physicians and Patients Should Question. Arthritis Care Res (Hoboken). 2013 March; 65(3): 329–339
13. Somers EC, Monrad SU, Warren JS, Solano M, Schnaas L, Hernandez-Avila M, Tellez-Rojo MM, Hu H. Antinuclear antibody prevalence in a general pediatric cohort from Mexico City: discordance between immunofluorescence and multiplex assays. Clin Epidemiol. 2016 Dec 20;9:1-8.
14. Cristian-Camilo Aragón et al. Anti-DFS70 antibodies: A new useful antibody in the exclusion of auto-immune diseases. Revista Colombiana de Reumatología. Volume 25, Issue 2, April–June 2018, Pages 104-111
15. Esha Das Gupta. Malaysian Family Physician 2009; Volume 4, Number 2&3 Common laboratory tests for rheumatological disorders: how do they helpthe diagnostic?
16.  Semin Arthritis Rheum Laboratory tests in the diagnosis and follow-up of pediatric rheumatic diseases: an update 2010 Aug;40(1):53-72
17. Alessandro Granito et al. Diagnostic role of anti-dsDNA antibodies: do not forget autoimmune hepatitis Nat Rev Rheumatol 2021 Apr;17(4):244.
18. Sita Naik. Laboratory tests and the paediatric rheumatologist: What does he need to know? Indian Journal of Rheumatology Volume 7, Issue 1, Supplement, May 2012, Pages 106-111
19. Fatih Haslak et al. Anti-nuclear antibody testing in children: How much is really necessary? Pediatr Int2021 Sep;63(9):1020-1025
20. Sujata Sawhney,Amita AggarwalPediatric Rheumatology Amita Aggarwal and Sujata Sawhney Chapter 10 Laboratory and the Pediatric Rheumatologist, pg 107-120
21. Mendez-Rayo T, Ochoa-Zárate L,Posso-Osorio I, Ortiz E,Naranjo-Escobar J, Tobón GJ. Interpretación de los autoanticuerpos en enfermedades reumatológicas Rev Colomb Reumatol.2018;25:112–125
22. Mihaela Spârchez   et al. Evaluation of anti-cyclic citrullinated peptide antibodies may be beneficial in RF-negative juvenile idiopathic arthritis patients. Clin Rheumatol 2016 Mar;35(3):601-7.
23. Alexandra Gireada, Nicolae Bacalbasa, Irina Balescu The ASO reaction – Clinical use and laboratory methods. Use and laboratory methods. REVISTA MEDICALÅ ROMÂNÅ – VOLUMUL LXII, NR. 3, An 2015
24. RAKESH KUMAR PILANIA, SURJIT SINGH Rheumatology Panel in Pediatric Practice INDIAN PEDIATRICS 407 VOLUME 56__MAY 15, 2019
25. ERNEST SURESH Laboratory tests in rheumatology: A rational approach CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 86 • NUMBER 3 MARCH 2019
26. Bita Shakoory et.al. The 2022 EULAR/ACR Points to Consider at the Early Stages of Diagnosis and Management of Suspected Haemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS). Arthritis & Rheumatology Vol. 75, No. 10, October 2023, pp 1714–1732
27. Lee, J.; Bae, K.S.; Rhim, J.W.;Lee, S.-Y.; Jeong, D.C.; Kang, J.H. Macrophage Activation Syndrome in Children: Update on Diagnosis and Treatment. Children 2024, 11, 755.
28. Crayne C, Cron RQ. Pediatric macrophage activation syndrome, recognizing the tip of the Iceberg. Eur J Rheumatol 2020; 7(Suppl 1): S13-S20.
29. Allen, C.E.; Yu, X.; Kozinetz, C.A.; McClain, K.L. Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosis. Pediatr. Blood Cancer 2008, 50, 1227–1235.
30. Sen, E.S.; Clarke, S.L.; Ramanan, A.V. Macrophage activation syndrome. Indian J. Pediatr. 2016, 83, 248–253.
31. Bagri, N.K.; Gupta, L.; Sen, E.S.; Ramanan, A.V. Macrophage activation syndrome in children: Diagnosis and management. Indian Pediatr. 2021, 58, 1155–1161.
32. Griffin, G.; Shenoi, S.; Hughes, G.C. Hemophagocytic lymphohistiocytosis: An update on pathogenesis, diagnosis, and therapy. Best Pract. Res. Clin. Rheumatol. 2020, 34, 101515.
33. Takakura, M.; Shimizu, M.; Irabu, H.; Sakumura, N.; Inoue, N.; Mizuta, M.; Nakagishi, Y.; Yachie, A. Comparison of serum biomarkers for the diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. Clin. Immunol. 2019, 208, 108252
34. Tangri N, Grams ME, Levey AS, et al. Multinational assessment of accuracy of equations for predicting risk of kidney failure: a metaanalysis. JAMA. 2016;315:164–174. 10. 
35. Tangri N, Stevens LA, Griffith J, et al. A predictive model for progression of chronic kidney disease to kidney failure. JAMA. 2011;305:1553–1559. 11. 
36. Delanaye P, Jager KJ, Bokenkamp A, et al. CKD: a call for an age-adapted definition. J Am Soc Nephrol. 2019;30:1785–1805
37. Seong Heon Kim. Renal involvement in pediatric rheumatologic diseases. Child Kidney Dis 2022;26(1):18-24
38. Jelusic M, Sestan M, Giani T and Cimaz R (2022) New Insights and Challenges Associated With IgA Vasculitis and IgA Vasculitis With Nephritis—Is It Time to Change the Paradigm of the Most Common Systemic Vasculitis in Childhood? Front. Pediatr. 10:853724
39. Sestan M, Srsen S, Kifer N, Sapina M, Batnozic Varga M, Ovuka A, et al. Persistence and severity of cutaneous manifestations in IgA vasculitis is associated with development of IgA vasculitis nephritis in children. Dermatology. (2021). doi: 10.1159/000516765.
40. Sestan M, Kifer N, Frkovic M, Sapina M, Srsen S, Batnozic Varga M. Gastrointestinal involvement and its association with the risk for nephritis in IgA vasculitis. Ther Adv Musculoskelet Dis. (2021) 13:1759720X211024828.
41. Stahl JL, Rutledge JC, Gordillo R. The unusual suspects: a curious case of acute kidney injury: answers. Pediatr Nephrol 2019;34:1213-5.
42. Francesca Ometto et al. Calprotectin in rheumatic diseases. Experimental Biology and Medicine 2017; 242: 859–873.
43. Rheumatology, 2024, 63, 26–33, Calprotectin: two sides of the same coin. Rheumatology, 2024, 63, 26–33
44. SCHULZE ZUR WIESCH A, FOELL D, FROSCH M, VOGL T, SORG C, ROTH J: Myeloid related proteins MRP8/MRP14 may predict disease flares in juvenile idiopathic arthritis. Clin Exp Rheumatol 2004; 22: 368-73
45. La C, Lê PQ, Ferster A, et al. Serum calprotectin (S100A8/A9): a promising biomarker in diagnosis  and follow- up in different  subgroups of juvenile idiopathic arthritis. RMD Open 2021;7:e001646.
46. Dirk Foell et al. A novel serum calprotectin (MRP8/14) particle-enhanced immuno-turbidimetric assay (sCAL turbo) helps to differentiate systemic juvenile idiopathic arthritis from other diseasesin routine clinical laboratory settings. Molecular and Cellular Pediatrics           (2023) 10:14  
47. A. Mariani et al. Serum calprotectin: a review of its usefulness and validity in paediatric rheumatic diseases. Clin Exp Rheumatol 2015; 33: 109-114.
48. Fautrel B, et al. EULAR/PReS recommendations for the diagnosis and management of Still’s disease, comprising systemic juvenile idiopathic arthritis and adult-onset Still’s disease. Ann Rheum Dis 2024;0:1–14.
49. Kozhevnikov AN. Serum Calprotectin like a Potential Serum Biomarker of Aggressive Erosive Course of Juvenile Arthritis. Research Article – (2022) Volume 11, Issue 2
50. ABE J, JIBIKI T, NOMA S, NAKAJIMA T, SAITO H, TERAI M: Gene expression profiling of the effect of highg- dose intravenous Ig in patients with Kawasaki disease. J Immunol 2005; 174: 5837-45.
51. KAWASAKI Y, OHARA S, ABE Y et al.: The role of serum myeloid-related protein 8/14 complex In Henoch–Schönlein purpura nephritis. Pediatr Nephrol 2012; 27: 65-71.