DOCK8 (Dedicator Of Cytokinesis 8)

We present a female paediatric patient with DOCK8 deficiency who was assessed for HSCT, but underwent liver transplantation fist in view of decompensated liver disease. The patient, unfortunately, succumbed secondary to infectious complications in the post-op period.

The patient was started on immunoglobulin infusions and dupilumab, with some improvement in his eczematous rash, before receiving a 100% matched unrelated-donor haematopoietic stem cell transplantation (HSCT)...However, the molecular link between DOCK8 deficiency and atopic skin inflammation remains unknown. This case highlights the importance of considering inborn errors of immunity in such cases of severe eczema associated with apparent immune dysregulation and susceptibility to recurrent infections.

Dupilumab is a safe and highly effective therapeutic option for pediatric patients with IEI-associated atopic manifestations, improving clinical outcomes, quality of life, and infection profile while preserving immune function. These findings support broader application of dupilumab in patients with IEI and warrant further investigation in larger, multicenter studies.

P2, N=70, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | N=128 --> 70 | Trial completion date: Dec 2026 --> Oct 2028 | Trial primary completion date: Dec 2025 --> Oct 2026

EBV-SMT may suggest an underlying immunodeficiency. Since the mortality is high, early genetic diagnosis of IEI, monitoring the patients with IEI for chronic EBV and cancer, and an individualized therapeutic approach will minimize complications.

Patients with defects in RAC2-associated regulators of actin usually present with late-onset symptoms due to normal immune profiles, but a higher rate of EBV and HPV infections, autoimmune cytopenia, asthma, and lymphoproliferation compared to defects in the CDC42 pathway. The severity of mutations in patients of the CDC42 group helps to estimate the prognosis of the disease and prioritization of HSCT.

Recovered microbial communities remained relatively stable through 1-year follow-up with clearance of oncogenic HPV and no convergence with transplant donors. These results highlight the immune system's critical role in restoring microbial balance and skin health.

P2, N=17, Recruiting, Johns Hopkins All Children's Hospital | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Jun 2026

We present a patient with advanced disease undergoing alloHSCT at the age of 11 years after individualized pre-treatment using dupilumab and rituximab resulting in a decrease in IgE levels and clinical improvement of the skin condition...Life-threatening infections, malignancy, and disease-related complications with organ damage pre-transplant are challenging in older DOCK8-deficient patients. The therapeutic role of dupilumab in DOCK8 deficiency should be evaluated in larger studies.

Proteins increased in COVID-19-associated sHLH, such as sPD-L1, and pathways, such as the syntaxin pathway, suggest important roles for the immune response in driving sHLH in the context of COVID-19.

This study of multiple cohorts identifies CHEK2 as a candidate susceptibility gene for DFSP. Additional epidemiologic and functional studies are needed to further characterize this potential gene-tumor relationship.

We present one of the largest single-center experiences on DOCK8 deficiency from India. A significant delay in the diagnosis contributed to poor outcomes in our cohort.