Researchers Identify Predictors of Intravenous Immunoglobulin Resistance in Patients With Kawasaki Disease

Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome, is an inflammatory disease that causes swelling in the walls of small-to-medium-sized blood vessels. KD is a rare disease that primarily occurs in children younger than 5 years old, and often targets their heart arteries.¹

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Common KD symptoms include high fever and swollen hands and feet with skin peeling. With early treatment, most patients recover and have no long-lasting problems. If left untreated, about one-fourth of patients will develop coronary artery lesions, which in severe cases can lead to stenosis and infarction.¹

Intravenous immunoglobulin (IVIG) is a concentrated pool of antibodies and serum proteins collected from many healthy blood donors that is used to treat a variety of diseases and conditions requiring immunomodulation.² In general, treatment with IVIG and aspirin is effective in patients with KD, although up to 27% of patients are resistant to IVIG. IVIG-resistant patients have an elevated risk for coronary artery lesions. The mechanism of IVIG resistance in KD is not understood and predictive biomarkers are needed.³

Researchers from the University of Electronic Science and Technology of China conducted a retrospective study that evaluated 771 children diagnosed with KD, 86 (11.2%) of whom were diagnosed with IVIG resistance. They assessed multiple clinical indicators and laboratory parameters in IVIG non-responders and IVIG responders.³

Their main objective was to assess the predictive value of the following inflammatory markers calculated from blood cell numbers³:

• Systemic immune inflammation index (SII): the product of the numbers of platelets and neutrophils divided by the number of lymphocytes.
• Systemic inflammation response index (SIRI): the product of the numbers of monocytes and neutrophils divided by the number of lymphocytes.
• Pan-immune inflammation value (PIV): the product of the numbers of monocytes, platelets, and neutrophils divided by the number of lymphocytes.

Clinical characteristic analysis showed a higher frequency of patients with extremity changes, tachypnea (fast, shallow breathing), expectoration, irritability, aseptic meningitis, and KD shock syndrome in the IVIG-resistant group.³

The researchers concluded from the laboratory parameter assessment that lymphocyte numbers and hemoglobin, serum sodium, and albumin concentrations were statistically significantly lower in IVIG-resistant patients. C-reactive protein, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, SII, SIRI, and PIV were all significantly higher in IVIG-resistant patients.³

According to the authors, the identification of composite inflammatory markers – SII, SIRI, and PIV – as independent risk factors for IVIG resistance is a novel observation that may aid clinical pediatricians in more accurately predicting IVIG-resistance in patients with KD. They suggested that these combined calculated ratios provide a more comprehensive evaluation of inflammation than individual blood cell measurements.³

The authors acknowledged multiple limitations of their work. The study was conducted at a single medical center, making it subject to inherent selection bias. It also had a small sample size and was missing data from some of the early cases. They concluded that a multi-center prospective study with a larger number of samples is needed to confirm the results and conclusions from this study.³

REFERENCES

1. Agarwal S, Agrawal DK. Kawasaki Disease: Etiopathogenesis and Novel Treatment Strategies. Expert Rev Clin Immunol. 2017;13(3): 247-258; doi:10.1080/1744666X.2017.1232165

2. Barahona Afonso AF, João CM. The Production Processes and Biological Effects of Intravenous Immunoglobulin. Biomolecules. 2016; 6(1):15; doi:10.3390/biom6010015

3. Yi C, Zhou Y-N, Guo J, Chen J, She X. Novel predictors of intravenous immunoglobulin resistance in patients with Kawasaki disease: a retrospective study. Front Immunol. 2024; doi: 10.3389/fimmu.2024.1399150