Relationship between vitamin D levels and intravenous immunoglobulin resistance in Kawasaki disease

Jun, Jae Sung; Jung, Young Kwon; Lee, Dong Won

doi:10.3345/kjp.2017.60.7.216

Cited by 18 publications

(23 citation statements)

References 27 publications

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“…Although a sudden increase in the incidence of Kawasaki disease (KD) was noted in the province of Bergamo, Italy, which was profoundly affected by the Covid-19 epidemics [44], another study reported a significant severe vitamin D deficiency in a cohort of 79 children with KD as compared to healthy controls, and low levels of vitamin D seems to correlate to the risk in developing coronary artery aneurysms (p = 0.005) and non-aneurysmatic cardiovascular lesions (p < 0.05) [45]. Moreover, vitamin D deficiency has been associated with resistance to intravenous immunoglobulin in KD (defined as persistent or recrudescent fever ≥ 36 h after the completion of the initial infusion), suggesting a potent immunomodulatory role of this vitamin [46]. Of note, most of the aforementioned studies could not define the optimal concentration of 25(OH) D and the corresponding dietary requirements or treatment regimen suitable to the given disease.…”

Section: Vitamin D In Autoimmune Diseasesmentioning

confidence: 99%

Possible role of vitamin D in Covid-19 infection in pediatric population

Panfili

Roversi

D’Argenio

et al. 2020

J Endocrinol Invest

118

116

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Purpose Covid-19 is a pandemic of unprecedented proportion, whose understanding and management is still under way. In the emergency setting new or available therapies to contrast the spread of COVID-19 are urgently needed. Elderly males, especially those affected by previous diseases or with comorbidities, are more prone to develop interstitial pneumonia that can deteriorate evolving to ARDS (acute respiratory distress syndrome) that require hospitalization in Intensive Care Units (ICUs). Even children and young patients are not spared by SARS-CoV 2 infection, yet they seem to develop a milder form of disease. In this setting the immunomodulatory role of Vitamin D, should be further investigated. Methods: We reviewed the literature about the immunomodulatory role of Vitamin D collecting data from the databases Medline and Embase. Results Vitamin D proved to interact both with the innate immune system, by activating Toll-like receptors (TLRs) or increasing the levels of cathelicidins and β-defensins, and adaptive immune system, by reducing immunoglobulin secretion by plasma cells and pro-inflammatory cytokines production, thus modulating T cells function. Promising results have been extensively described as regards the supplementation of vitamin D in respiratory tract infections, autoimmune diseases and even pulmonary fibrosis. Conclusions In this review, we suggest that vitamin D supplementation might play a role in the prevention and/or treatment to SARS-CoV-2 infection disease, by modulating the immune response to the virus both in the adult and pediatric population.

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Section: Vitamin D In Autoimmune Diseasesmentioning

confidence: 99%

Possible role of vitamin D in Covid-19 infection in pediatric population

Panfili

Roversi

D’Argenio

et al. 2020

J Endocrinol Invest

118

116

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“…Additionally, Jun et al retrospectively reviewed whether low vitamin D levels were associated with resistance to IVIG therapy in KD cases. They found vitamin D deficiency to be associated with IVIG resistance, but not associated with inflammatory markers [26]. In summary, we conclude that vitamin D could potentially play a role in the inflammatory process of KD.…”

Section: Discussionmentioning

confidence: 47%

Breastfeeding and vitamin D supplementation reduce the risk of Kawasaki disease in a German population-based case-control study

et al. 2019

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Background In Kawasaki disease (KD), a vasculitis of unknown etiology, the most serious complication is the development of coronary artery aneurysm (CAA). To date, the exact pathomechanism of KD is unknown. Both environmental and genetic factors seem to be associated with the development of the disease. Methods Data on KD patients recruited from the population-based German Pediatric Surveillance Study during 2012–2014 were used to evaluate the impact of various factors from the perinatal and infancy period on the development of KD. The study design was a matched case-control study with respect to age, sex and place of residence ( n = 308 KD cases, n = 326 controls). All KD patients were individually re-evaluated; all fulfilled the international diagnostic KD criteria. A standardized questionnaire was used to review breastfeeding practices, vitamin D supplementation and birth characteristics. Logistic regression analyses were performed to obtain odds ratios (OR) for various risk factors among the case-control pairs. Simple measures of association were used to assess the impact of these factors on the clinical course. Results There was no difference in lengths of gestation, birth weight or parturition between KD patients and controls, but independently from each other vitamin D supplementation and breastfeeding were negatively associated with KD, even when adjusted for age, place of residence and sex. The duration of vitamin D was significantly shorter among children with KD than among children without KD ( p = 0.039, OR = 0.964, 95% CI: 0.931–0.998), as was the duration of breastfeeding ( p = 0.013, OR = 0.471, 95% CI: 0.260–0.853). Comparing KD patients with and without breastfeeding and/or vitamin D supplementation, there were no differences regarding developing CAA, being refractory to intravenous immunoglobulin treatment, age at onset of the disease and levels of inflammatory laboratory values. Conclusion Our findings indicate breastfeeding and vitamin D supplementation to have protective effects in association with KD in our study population; however, these seem not to influence the natural course of the disease. Although the overall effects were relatively small, they nevertheless underline the overall benefit of both interventions. Trial registration Clinical Trial Registration: German clinical trial registration, http://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00010071 . Date of registration was 26. February 2016. The trial was registered retrospectively. Electronic supplementary material The online version of this article (10.1186/s12887-019-1438-2) contains supplementary material, which is available to authorized users.

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“…However, later randomized trials demonstrated no significant effects on the severity or fatality of COVID-19 (128). Taken together, aiming at a single target of one cytokine action may be ineffective but a combined regimen or sequential targeting may be required for eliminating the cytokine storm mediated by a couple of hyperinflammatory cytokines in COVID-19 or MIS-C. Th17 mediators, Il-6 and IL-17A and Th1 down-stream mediators, TNF-α and IP-10, more prominently increased in KD than in MIS-C (27,28,45,108) (115)(116)(117)(129)(130)(131). Vitamin D levels have been shown lower in many patients with COVID-19 and associated with increased inflammatory cytokines and an increased risk of pneumonia (129).…”

Section: Therapeutic Perspectives Of Mis-cmentioning

confidence: 99%

“…Taken together, aiming at a single target of one cytokine action may be ineffective but a combined regimen or sequential targeting may be required for eliminating the cytokine storm mediated by a couple of hyperinflammatory cytokines in COVID-19 or MIS-C. Th17 mediators, Il-6 and IL-17A and Th1 down-stream mediators, TNF-α and IP-10, more prominently increased in KD than in MIS-C (27,28,45,108) (115)(116)(117)(129)(130)(131). Vitamin D levels have been shown lower in many patients with COVID-19 and associated with increased inflammatory cytokines and an increased risk of pneumonia (129). The lower vitamin D concentration is not only linked to higher severity of COVID-19 (130,131), but also associated with an increase in thrombotic episodes (132,133), which are frequently observed in COVID-19 associated MIS-C (4-9).…”

Section: Therapeutic Perspectives Of Mis-cmentioning

confidence: 99%

“…Both genetic and epigenetic alterations in Treg pathways have been demonstrated in patients with KD ( 53 – 56 ). The induction and/or stabilization of Treg cell development is affected by endogenous milieu, such as vitamins and metabolites from microbiota ( 115 – 117 , 129 – 131 ). Vitamin D levels have been shown lower in many patients with COVID-19 and associated with increased inflammatory cytokines and an increased risk of pneumonia ( 129 ).…”

Section: Mechanistic Immunotherapies Of Mis-c Based On Infection Immumentioning

confidence: 99%

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Phenotype, Susceptibility, Autoimmunity, and Immunotherapy Between Kawasaki Disease and Coronavirus Disease-19 Associated Multisystem Inflammatory Syndrome in Children

et al. 2021

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Coronavirus disease-19 (COVID-19) in children is usually mild but some are susceptible to a Kawasaki disease (KD)-like multisystem inflammatory syndrome in children (MIS-C) in the convalescent stage, posing a need to differentiate the phenotype, susceptibility, autoimmunity, and immunotherapy between KD and MIS-C, particularly in the upcoming mass vaccination of COVID-19. Patients with MIS-C are prone to gastrointestinal symptoms, coagulopathy, and shock in addition to atypical KD syndrome with fever, mucocutaneous lesions, lymphadenopathy, and/or cardiovascular events. MIS-C manifests KD-like symptoms that alert physicians to early recognize and adopt the KD treatment regimen for patients with MIS-C. MIS-C linked to COVID-19 teaches us infection-associated autoimmune vasculitis and vice versa. Studies on genetic susceptibility have identified certain human leukocyte antigen (HLA) locus and toll-like receptor (TLR) associated with KD and/or COVID-19. Certain HLA subtypes, such as HLA-DRB1 and HLA-MICA A4 are associated with KD. HLA-B*46:01 is proposed to be the risk allele of severe COVID-19 infection, and blood group O type is a protective factor of COVID-19. The autoimmune vasculitis of KD, KD shock syndrome (KDSS), or MIS-C is mediated by a genetic variant of HLA, FcγR, and/or antibody-dependent enhancement (ADE) resulting in hyperinflammation with T helper 17 (Th17)/Treg imbalance with augmented Th17/Th1 mediators: interleukin-6 (IL-6), IL-10, inducible protein-10 (IP-10), Interferon (IFNγ), and IL-17A, and lower expression of Treg-signaling molecules, FoxP3, and transforming growth factor (TGF-β). There are certain similarities and differences in phenotypes, susceptibility, and pathogenesis of KD, KDSS, and MIS-C, by which a physician can make early protection, prevention, and precision treatment of the diseases. The evolution of immunotherapies for the diseases has shown that intravenous immunoglobulin (IVIG) alone or combined with corticosteroids is the standard treatment for KD, KDSS, and MIS-C. However, a certain portion of patients who revealed a treatment resistance to IVIG or IVIG plus corticosteroids, posing a need to early identify the immunopathogenesis, to protect hosts with genetic susceptibility, and to combat Th17/Treg imbalance by anti-cytokine or pro-Treg for reversal of the hyperinflammation and IVIG resistance. Based on physiological and pathological immunity of the diseases under genetic susceptibility and host milieu conditions, a series of sequential regimens are provided to develop a so-called “Know thyself, enemy (pathogen), and ever-victorious” strategy for the prevention and immunotherapy of KD and/or MIS-C.

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Relationship between vitamin D levels and intravenous immunoglobulin resistance in Kawasaki disease

Cited by 18 publications

References 27 publications

Possible role of vitamin D in Covid-19 infection in pediatric population

Possible role of vitamin D in Covid-19 infection in pediatric population

Breastfeeding and vitamin D supplementation reduce the risk of Kawasaki disease in a German population-based case-control study

Phenotype, Susceptibility, Autoimmunity, and Immunotherapy Between Kawasaki Disease and Coronavirus Disease-19 Associated Multisystem Inflammatory Syndrome in Children

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