Gastric cancer, inflammatory bowel disease and polyautoimmunity in a 17-year-old boy: CTLA-4 deficiency successfully treated with Abatacept

Abstract

Gut involvement is frequent in immunologic disorders, especially with inflammatory manifestations but also with cancer. In the last years, advances in functional and genetic testing have improved the diagnostic and therapeutic approach to immune dysregulation syndromes. CTLA-4 deficiency is a rare disease with variable phenotype, ranging from absence of symptoms to severe multisystem manifestations and complications. We describe a rare case of CTLA-4 deficiency in a boy with gastric cancer, very early onset inflammatory bowel disease and polyautoimmunity, the second-ever reported in the literature with the same characteristics. A 17-year-old boy was referred to Bambino Gesù Children’s Hospital of Rome, a tertiary care center, for a gastric mass and a long-term history of very early onset inflammatory bowel disease, diabetes mellitus type 1, polyarthritis and psoriasis. Histology of gastric biopsies revealed the presence of neoplastic signet ring cells. Imaging staging showed localized cancer; therefore, the patient underwent subtotal gastrectomy with termino-lateral gastro-jejunal anastomosis. Immunological work up and genetic testing by next-generation sequencing panels for primary immunodeficiencies led to the diagnosis of CTLA-4 deficiency. Good disease control was obtained with the administration of Abatacept. The patient experienced an asymptomatic SARS-CoV-2 infection without any concern. Eighteen months after treatment initiation, the patient is alive and well. Immunologic and genetic testing, such as next-generation sequencing, should always be part of the diagnostic approach to patients with complex immune dysregulation syndrome, severe clinical course, poor response to treatments or cancer. The early recognition of the monogenic disease is the key for disease management and targeted therapy.

COVID-19-related health outcomes in people with primary immunodeficiency: A systematic review

“…A total of 459 people with PI and COVID-19 are described from 54 of the 68 studies [ 12 , 13 , 16 , [18] , [19] , [20] , [21] , 24 , 26 , 27 , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] ] (Table 2). These cases came from case reports as well as cohort studies with information available for individual patients.…”

Inborn Errors of Immunity in Children with Autoimmune and Allergic Complaints: A Single Center Experience from Diagnosis to Treatment

“…Abatacept was well-tolerated, but allowed for only a mild reduction of glucocorticoids dosage, which was not enough to change the course of her disease, with death following two years after the start of treatment. Recent case reports described the effective use of abatacept to treat pediatric patients with either autoimmune or autoinflammatory manifestations and an underlying CTLA4 deficiency [13][14][15]. Another case, a girl with autoimmune thyroiditis, gastritis, oral ulcerations and mucosal candidiasis, with positive antinuclear and anti-DNA antibodies, was treated with hydroxychloroquine based on a diagnosis of Systemic Lupus Erythematosus, with scarce control of symptoms.…”

Severity of SARS-CoV-2 infection in children with inborn errors of immunity (primary immunodeficiencies): a systematic review

“…The detailed characteristics of the included studies are shown in Additional file 2 : Table S3. There were 73 case report [ 4 – 6 , 8 , 9 , 25 – 32 , 37 – 39 , 44 , 45 , 49 , 51 , 53 – 60 , 67 – 69 , 72 , 76 – 79 , 82 – 84 , 86 – 88 , 90 , 91 , 93 , 94 , 96 , 99 – 107 , 109 – 114 , 116 , 119 – 123 , 126 , 127 , 129 – 131 ], 38 cohort [ 7 , 10 , 19 , 33 – 36 , 40 – 43 , 46 – 48 , 50 , 52 , 61 – 66 , 70 , 71 , 73 , 74 , 80 , 81 , 92 , 95 , 97 , 98 , 108 , 117 , 118 , 124 , 125 , 132 ], 4...…”

“…Only six studies were made within multi-countries (n = 6) [ 10 , 33 , 35 , 51 , 95 , 132 ]. The majority of the studies were single centre [ 4 – 6 , 8 , 9 , 19 , 25 – 32 , 34 , 37 – 39 , 41 , 43 – 47 , 49 , 50 , 52 – 60 , 62 , 64 , 66 – 69 , 71 , 72 , 75 – 80 , 82 – 84 , 86 – 90 , 93 , 94 , 96 , 98 – 117 , 119 – 131 ] and only 23 studies were multi-centre [ 7 , 10 , 33 , 35 , 36 , 40 , 42 , 48 , 51 , 61 , 63 , 65 , 70 , 73 , 74 , 81 , 85 , 91 , 92 , 95 , 97 , 118 , 132 ]. Among all included studies in our systematic review, only one study reported on the other potential modifiers in immunity-related pathways for all diagnosed IEIs in children who were infected with SARS-CoV-2 (n = 1, 0.9%) […”