In recent years, the knowledge about the immune-mediated impairment of bone marrow precursors in immune-dysregulation and autoimmune disorders has increased. In addition, immune-dysregulation, secondary to marrow failure, has been reported as being, in some cases, the most evident and early sign of the disease and making the diagnosis of both groups of disorders challenging. Dyskeratosis congenita is a disorder characterized by premature telomere erosion, typically showing marrow failure, nail dystrophy and leukoplakia, although incomplete genetic penetrance and phenotypes with immune-dysregulation features have been described. We report on a previously healthy 17-year-old girl, with a cousin successfully treated for acute lymphoblastic leukemia, who presented with leukopenia and neutropenia. The diagnostic work-up showed positive anti-neutrophil antibodies, leading to the diagnosis of autoimmune neutropenia, a slightly low NK count and high TCR-αβ+-double-negative T-cells. A next-generation sequencing (NGS) analysis showed the 734C>A variant on exon 6 of the TINF2 gene, leading to the p.Ser245Tyr. The telomere length was short on the lymphocytes and granulocytes, suggesting the diagnosis of an atypical telomeropathy showing with immune-dysregulation. This case underlines the importance of an accurate diagnostic work-up of patients with immune-dysregulation, who should undergo NGS or whole exome sequencing to identify specific disorders that deserve targeted follow-up and treatment.

Evans syndrome (ES) is a rare disorder classically defined as the simultaneous or sequential presence of autoimmune haemolytic anaemia and immune thrombocytopenia, but it has also been described as the presence of at least two autoimmune cytopenias. Recent reports have shown that ES is often a manifestation of an underlying inborn error of immunity (IEI) that can benefit from specific treatments.
The aim of this study is to investigate the clinical and immunological characteristics and the underlying genetic background of a single-centre cohort of patients with ES.
Data were obtained from a retrospective chart review of patients with a diagnosis of ES followed in our centre. Genetic studies were performed with NGS analysis of 315 genes related to both haematological and immunological disorders, in particular IEI.
Between 1985 and 2020, 40 patients (23 men, 17 women) with a median age at onset of 6 years (range 0-16) were studied. ES was concomitant and sequential in 18 (45%) and 22 (55%) patients, respectively. Nine of the 40 (8%) patients had a positive family history of autoimmunity. Other abnormal immunological features and signs of lymphoproliferation were present in 24/40 (60%) and 27/40 (67%) of cases, respectively. Seventeen out of 40 (42%) children fit the ALPS diagnostic criteria. The remaining 21 (42%) and 2 (5%) were classified as having an ALPS-like and an idiopathic disease, respectively. Eighteen patients (45%) were found to have an underlying genetic defect on genes FAS, CASP10, TNFSF13B, LRBA, CTLA4, STAT3, IKBGK, CARD11, ADA2, and LIG4. No significant differences were noted between patients with or without variant and between subjects with classical ES and the ones with other forms of multilineage cytopenias.
This study shows that nearly half of patients with ES have a genetic background being in most cases secondary to IEI, and therefore, a molecular evaluation should be offered to all patients.

BACKGROUND: Autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), and autoimmune neutropenia (AIN) are reported in the literature after liver, intestinal, heart, pancreas, and kidney transplants. We report a case of autoimmune pancytopenia (AIHA, AIN and ITP) 9 years after liver transplantation with confirmed erythrocyte and neutrophil auto-antibodies.
METHODS: A 49 years old man was admitted to our hospital presented with dysentery and fever, with history of liver transplantation in 2008. Laboratory evaluation demonstrated hemoglobin: 7.2 g/dL, granulocytes: 0.10 × 109/L and platelets: 15 × 109/mm³; indirect bilirubin: 3.62 mg/dL; lactate dehydrogenase: 603 U/L. Direct antiglobulin test revealed a monospecific anti-IgG plus C3 and the acid eluate was reactive to all panel red cells, consistent with an AIHA. Granulocyte immunofluorescence test (GIFT) and agglutination test (GAT) were reactive for granulocytes. Test with Luminex technology for human neutrophil antigen (HNA) antibody detection was strong reactive with beads expressing HNA-1a, -1b, -1c, -2, -4a and -5a antigens. HNA genotyping revealed the presence of the corresponding antigens, confirming the autoantibodies. Test with Luminex technology for human leucocyte antigen (HLA) antibody detection was negative. Monoclonal antibody immobilization of platelet antigens (MAIPA) assay was negative. Viral causes were excluded. The condition was compatible with clinical onset of autoimmune pancytopenia. Prednisone was administered at an initial dose of 1 mg/kg/day and immunosuppressive therapy was adjusted. This treatment resulted in rapid resolution of pancytopenia.
CONCLUSIONS: Combined autoimmune pancytopenia (AIHA, AIN and ITP) is a rare condition that may occur after liver transplantation. Early recognition of this phenomenon permits appropriate treatment.