Relationship between T-cell HLA-DR expression and intravenous immunoglobulin treatment response in Kawasaki disease

Wakiguchi, Hiroyuki; Hasegawa, Shunji; Suzuki, Yasuo; Kudo, Kazuhiko; Ichiyama, Takashi

doi:10.1038/pr.2015.12

Cited by 27 publications

(15 citation statements)

References 37 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well known that KD is associated with increased immune system activation, increased complement activation, and increased antibody‐dependent cell‐mediated cytotoxicity, all of which could theoretically lead to increased hemolysis. Patients with refractory KD in particular have increased interleukin (IL)‐1 levels, increased CRP, and increased neutrophil percentage, markers of T‐cell activation such as increased T‐cell HLA‐DR expression, lack of reduction of soluble IL‐2 receptor, and IL‐6 in response to IVIG . The relationship between inflammation and hemolysis in our cohort was not straightforward, as there was not a clear difference between the levels of inflammatory markers ESR and CRP at presentation in patients who did and did not develop hemolysis.…”

Section: Discussionmentioning

confidence: 80%

“…Patients with refractory KD in particular have increased interleukin (IL)-1 levels, increased CRP, and increased neutrophil percentage, 21 markers of Tcell activation such as increased T-cell HLA-DR expression, lack of reduction of soluble IL-2 receptor, and IL-6 in response to IVIG. [23][24][25] The relationship between inflammation and hemolysis in our cohort was not straightforward, as there was not a clear difference between the levels of inflammatory markers ESR and CRP at presentation in patients who did and did not develop hemolysis. Macrophage activation syndrome (MAS) is an important complication of KD that may manifest with an acute decrease in Hb and may be underrecognized.…”

Section: Discussionmentioning

confidence: 86%

See 1 more Smart Citation

High‐dose intravenous immunoglobulin is strongly associated with hemolytic anemia in patients with Kawasaki disease

et al. 2018

View full text Add to dashboard Cite

BACKGROUND Hemolysis is a reported side effect of intravenous immunoglobulin (IVIG) therapy in adults, but pediatric data are scarce. We determined the frequency of IVIG‐associated hemolysis in patients with Kawasaki disease (KD) and characterized risk factors for hemolysis. We hypothesized that hemolysis is more common in children with KD than adults with other disorders, and hemolysis risk is related to IVIG dose and degree of inflammation. STUDY DESIGN AND METHODS This was an 8‐year, single‐center, retrospective cohort study. A total of 419 KD patients were identified; 123 had pre‐ and post‐treatment complete blood counts allowing for assessment of anemia. Hemolytic anemia was defined as decrease in hemoglobin after IVIG greater than 1 g/dL with immunohematologic or biochemical studies supporting hemolysis. RESULTS 123 patients were stratified as having hemolysis (n = 18, 15%) or nonhemolysis (n = 105, 85%). Patients with hemolysis were more likely to have complete versus incomplete KD (65% vs. 39%, p = 0.04) and refractory versus nonrefractory course (78% vs. 16%, p < 0.001). Patients receiving 4 g/kg versus 2 g/kg IVIG were more likely to hemolyze (89% vs. 34%, p < 0.001). Patients with hemolysis had mostly non‐O blood group (94%), positive direct antiglobulin tests (89%), and positive eluates (72%). Two‐thirds of patients with hemolysis required RBC transfusion. CONCLUSIONS Hemolysis occurred in 15% of KD patients evaluated for anemia and is strongly associated with high‐dose (4 g/kg) IVIG. KD patients receiving high‐dose IVIG should have close hematologic monitoring to identify hemolysis.

show abstract

Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 86%

High‐dose intravenous immunoglobulin is strongly associated with hemolytic anemia in patients with Kawasaki disease

et al. 2018

View full text Add to dashboard Cite

show abstract

“…However, there has been no report in which any aggressive therapy prevented coronary artery lesions in patients at high risk of unresponsiveness predicted by biomarkers and genetic variants. For more information about studies of biomarkers and genetic variants, two recent reviews are informative [74,75] . More-aggressive initial treatment for patients at a high risk of IVIG unresponsiveness after risk stratification using a predictive model has been recommended in the recently updated guidelines for the medical treatment of acute Kawasaki disease in Japan [39] .…”

Section: Combination With Ivig As the Routine First Line Treatmentmentioning

confidence: 99%

Use of corticosteroids during acute phase of Kawasaki disease

Yu¹

2015

WJCP

View full text Add to dashboard Cite

In spite of initial intravenous immunoglobulin (IVIG) treatment, a significant number of patients are unresponsive to it and are at a higher risk for coronary artery lesions. Corticosteroids have been used as a secondary drug or used in combination with IVIG. Three options of using corticosteroids for the treatment of patients during the acute phase of Kawasaki disease, have been considered. The first is their use exclusively for patients unresponsive to IVIG treatment. The second is their use in combination with IVIG as the routine first line therapy for all patients. The last is the use in the combination as the first line therapy for selected patients at a high risk being unresponsive to initial IVIG. However, it is uncertain that the corticosteroids as the second line treatment are better than the additional IVIG in patients unresponsive to initial IVIG. The combination of corticosteroids and IVIG as the routine first line therapy also have not enough evidences. The last option of using corticosteroids - the combination of corticosteroids and IVIG in patients at high risk of unresponsiveness, is a properly reasonable treatment strategy. However, there have been no globally standardized predictive models for the unresponsiveness to initial IVIG treatment. Therefore, future investigations to determine the best predictive model are necessary.

show abstract

“…Circulating monocyte/macrophages, rather than T cells, are reported to be activated during the acute phase of KD . We have reported that increased HLA‐DR expression on CD4 + T cells or CD8 + T cells is associated with IVIG resistance in KD patients . Repeated IVIG could sufficiently control the activation of monocytes/macrophages or coronary arterial endothelial cells but not the activation of T cells .…”

Section: Discussionmentioning

confidence: 96%

“…1 We have reported that increased HLA-DR expression on CD4 + T cells or CD8 + T cells is associated with IVIG resistance in KD patients. 15 Repeated IVIG could sufficiently control the activation of monocytes/macrophages or coronary arterial endothelial cells but not the activation of T cells. 1 With regard to this, a shift to T cell activation might account for the pathophysiology of refractory KD in young infants.…”

Section: Discussionmentioning

confidence: 99%

Adjunct cyclosporine therapy for refractory Kawasaki disease in a very young infant

Okada

Azuma

Suzuki

et al. 2015

Pediatrics International

Self Cite

View full text Add to dashboard Cite

Herein we describe the case of a 6-week-old boy who developed complete Kawasaki disease (KD). The cytokine profile and activation of monocytes and subsequent T cells matched the typical feature of refractory KD. The patient received a total of three courses of i.v. immunoglobulin (IVIG), but did not achieve clinical relief. Adjunctive therapy with oral cyclosporine A (CsA) led to prompt defervescence. This was continued for 7 days without serious adverse events. Coronary artery dilatations regressed within 3 months of follow up. KD infants <3 months of age are at higher risk of coronary artery aneurysm than the older ones. To our knowledge, oral CsA treatment has not been reported in such young infants with KD. The diagnosis and treatment of very young infants with KD are challenging. Adjunctive use of CsA in IVIG treatment could be effective for refractory KD in infants <3 months of age.

show abstract

Relationship between T-cell HLA-DR expression and intravenous immunoglobulin treatment response in Kawasaki disease

Cited by 27 publications

References 37 publications

High‐dose intravenous immunoglobulin is strongly associated with hemolytic anemia in patients with Kawasaki disease

High‐dose intravenous immunoglobulin is strongly associated with hemolytic anemia in patients with Kawasaki disease

Use of corticosteroids during acute phase of Kawasaki disease

Adjunct cyclosporine therapy for refractory Kawasaki disease in a very young infant

Contact Info

Product

Resources

About