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Case Report: Refractory Autoimmune Gastritis Responsive to Abatacept in LRBA Deficiency.

ABSTRACT: Primary immunodeficiency (PID) with immune dysregulation may present with early onset gastrointestinal autoimmune disorders. When gastrointestinal autoimmunity is associated with multiple extraintestinal immune system dysfunction the diagnosis of PID is straightforward. However, with the advent of next generation sequencing technologies, genetic defects in PID genes have been increasingly recognized even when a single or no extraintestinal signs of immune dysregulation are present. A genetic diagnosis is especially important considering the expanding armamentarium of therapies designed to inhibit specific molecular pathways. We describe a boy with early-onset severe, refractory autoimmune gastritis and biallelic mutations in the LRBA gene causing a premature STOP-codon who was successfully treated with CTLA4-Ig, abatacept, with long term clinical and endoscopic remission. The case underscores the importance to consider a monogenetic defect in early onset autoimmune disorders, since the availability of targeted treatments may significantly improve patient prognosis.

SUBMITTER: Boz V

PROVIDER: S-EPMC7952427 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Case Report: Refractory Autoimmune Gastritis Responsive to Abatacept in LRBA Deficiency.

Boz Valentina V Valencic Erica E Girardelli Martina M Pin Alessia A Gàmez-Diaz Laura L Tommasini Alberto A Lega Sara S Bramuzzo Matteo M

Frontiers in immunology 20210226

Primary immunodeficiency (PID) with immune dysregulation may present with early onset gastrointestinal autoimmune disorders. When gastrointestinal autoimmunity is associated with multiple extraintestinal immune system dysfunction the diagnosis of PID is straightforward. However, with the advent of next generation sequencing technologies, genetic defects in PID genes have been increasingly recognized even when a single or no extraintestinal signs of immune dysregulation are present. A genetic dia ...[more]

PMID: 33717114

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Project description:BackgroundLPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency disease (PID) characterized by a regulatory T cell defect resulting in immune dysregulation and autoimmunity. We present two siblings born to consanguineous parents of North African descent with LRBA deficiency and central nervous system (CNS) manifestations. As no concise overview of these manifestations is available in literature, we compared our patient's presentation with a reviewed synthesis of the available literature.Case presentationsThe younger brother presented with enteropathy at age 1.5 years, and subsequently developed Evans syndrome and diabetes mellitus. These autoimmune manifestations led to the genetic diagnosis of LRBA deficiency through whole exome sequencing with PID gene panel. At 11 years old, he had two tonic-clonic seizures. Brain MRI showed multiple FLAIR-hyperintense lesions and a T2-hyperintense lesion of the cervical medulla. His sister presented with immune cytopenia at age 9 years, and developed diffuse lymphadenopathy and interstitial lung disease. Genetic testing confirmed the same mutation as her brother. At age 13 years, a brain MRI showed multiple T2-FLAIR-hyperintense lesions. She received an allogeneic hematopoietic stem cell transplantation (allo-HSCT) 3 months later. Follow-up MRI showed regression of these lesions.ConclusionsNeurological disease is documented in up to 25% of patients with LRBA deficiency. Manifestations range from cerebral granulomas to acute disseminating encephalomyelitis, but detailed descriptions of neurological and imaging phenotypes are lacking. LRBA deficiency amongst other PIDs should be part of the differential diagnosis in patients with inflammatory brain lesions. We strongly advocate for a more detailed description of CNS manifestations in patients with LRBA deficiency, when possible with MR imaging. This will aid clinical decision concerning both anti-infectious and anti-inflammatory therapy and in considering the indication for allo-HSCT.

Project description:BackgroundIpilimumab is a cytotoxic T-lymphocyte-associated protein 4 receptor antibody used for immunotherapy in cancer. Several immune-related adverse events are known. Steroid responsive encephalopathy associated with autoimmune thyroiditis is an autoimmune encephalopathy associated with Hashimoto's Disease and elevated serum levels of the related antibodies (anti-thyroid-peroxidase antibody or anti-thyroglobulin antibody). Our case implies that steroid responsive encephalopathy associated with autoimmune thyroiditis may be another previously unreported side effect of ipilimumab therapy.Case presentationWe report the case of a 64 years old caucasian patient with prostatic cancer who received ipilimumab therapy in a clinical trial. He presented with aphasia, tremor and ataxia, myocloni, hallucinations, anxiety and agitation in turns with somnolence. Cranial nerves, deep tendon reflexes, motor and sensory functions were normal. Electroencephalography showed background slowing but no epileptic discharges. Brain magnetic resonance imaging was normal and showed no signs of hypophysitis. Cerebrospinal fluid findings ruled out infection and neoplastic meningitis. Anti-thyroid antibodies (anti-thyroid-peroxidase antibody and anti-thyroglobulin antibody) were heavily increased. Assuming steroid responsive encephalopathy associated with autoimmune thyroiditis the patient was treated with 1,000 mg methylprednisolone i.v. for 3 days and continued with 1 mg/kg orally. On the 3rd day of treatment the patient's condition started to improve. Within the next few days he gradually returned to his previous state, and electroencephalography eventually showed only slight slowing. Seven months later the patient's condition was stable, and anti-thyroid antibodies were no more detectable.ConclusionSteroid responsive encephalopathy associated with autoimmune thyroiditis may be a hitherto unrecognized complication of ipililumab treatment and should be taken into consideration in patients developing central nervous symptoms undergoing this treatment.

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Case Report: Refractory Autoimmune Gastritis Responsive to Abatacept in LRBA Deficiency.

Publications

Case Report: Refractory Autoimmune Gastritis Responsive to Abatacept in LRBA Deficiency.

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