Publications by authors named "Kai Lehmberg"
Article Synopsis
- Patients with JAGN1 mutations experience severe congenital neutropenia, leading to high rates of bacterial infections and poor response to G-CSF therapy.
- Two unrelated patients, one pregnant and one an infant, received GM-CSF after G-CSF failure, but neither showed an increase in neutrophil counts and treatment was eventually stopped due to further declines and infections.
- Despite the promising results in a mouse model, GM-CSF therapy did not benefit the patients, highlighting the need for early evaluation for hematopoietic stem cell transplantation in these cases.
Hemophagocytic lymphohistiocytosis (HLH) has been described for decades in association with malignancies (M-HLH). While its mechanism is unknown, M-HLH has a poor prognosis, ranging from 10% to 30% overall survival. Mature T-cell lymphomas, diffuse large B-cell lymphoma, and Hodgkin lymphoma, with or without viral co-triggers such as Epstein-Barr virus, are among the most frequent underlying entities.
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- The study analyzed the current diagnostic criteria for familial hemophagocytic lymphohistiocytosis (FHL) and aimed to improve them through a case-control approach involving 366 children with genetic FHL or Griscelli syndrome.
- It compared the existing HLH-2004 criteria's effectiveness with a new optimal model based on 17 variables, finding similar diagnostic thresholds with high accuracy rates (99.1% overall).
- The researchers concluded that while the HLH-2004 criteria are valid, additional cellular and genetic assays are beneficial for confirming diagnoses, particularly in differentiating FHL from severe infections or systemic-onset juvenile idiopathic arthritis.
() is a significant human pathogen, in particular in patients with an underlying medical condition. It is equipped with a large variety of virulence factors enabling both colonization and invasive disease. The spectrum of manifestation is broad, ranging from superficial skin infections to life-threatening conditions like pneumonia and sepsis.
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- The study investigates autoimmune lymphoproliferative syndrome (ALPS) and similar severe conditions characterized by lymphoproliferation and autoimmune cytopenias, aiming to better classify these disorders based on genetic and clinical features.
- Conducted in Germany with 431 children referred for ALPS evaluation, the study categorized patients based on specific criteria related to lymphoproliferation and associated immune deficiencies, with a median diagnostic age of about 9.8 years.
- Findings revealed that 55% of enrolled children were diagnosed with ALPS, and genetic assessments helped differentiate ALPS from autoimmune lymphoproliferative syndrome-like diseases, enhancing understanding and classification of these immune disorders.
Primary hemophagocytic lymphohistiocytosis (pHLH) is a life-threatening hyperinflammatory syndrome that develops mainly in patients with genetic disorders of lymphocyte cytotoxicity and X-linked lymphoproliferative syndromes. Previous studies with etoposide-based treatment followed by hematopoetic stem cell transplantation (HSCT) resulted in 5-year survival of 50% to 59%. Contemporary data are lacking.
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- Inborn errors of immunity (IEI) lead to immune dysfunction, causing increased risks of infections and diseases like cancer, as seen in a consanguineous family with Hodgkin lymphoma and severe immune issues.
- Family members showed variable weaknesses in natural killer (NK) cells and cytotoxic T cell functions, and genetic analysis revealed harmful variants linked to specific disorders.
- The study suggests that these genetic variants may worsen immune responses and overall disease severity, highlighting the importance of understanding genetic interactions for effective treatment strategies.
Article Synopsis
- - The TREC-based newborn screening for severe combined immunodeficiencies (SCID) was implemented in Germany in August 2019, with assessments conducted every six months for 2.5 years to evaluate its effectiveness.
- - Out of 1.9 million newborns screened, 88 cases of congenital T-cell lymphocytopenia were identified, including 25 SCID cases, and 88% were successfully genetically diagnosed.
- - The newly established API-CID network enhances patient tracking and treatment, showing excellent short-term outcomes from hematopoietic stem cell transplantation, but ongoing assessments will be crucial for understanding long-term results.
Most hereditary forms of hemophagocytic lymphohistiocytosis (HLH) are caused by defects of cytotoxicity, including the vesicle trafficking disorder Griscelli syndrome type 2 (GS2, RAB27A deficiency). Deficiency of the mitogen-activated protein kinase activating death domain protein (MADD) results in a protean syndrome with neurological and endocrinological involvement. MADD acts as a guanine nucleotide exchange factor for small guanosine triphosphatases, including RAB27A.
View Article and Find Full Text PDFHemophagocytic lymphohistiocytosis (HLH; hemophagocytic syndrome) is a rare syndrome of potentially fatal, uncontrolled hyperinflammation. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is indicated in primary, recurrent or progressive HLH, but information about its outcomes in the adult population is limited. We obtained data about 87 adult (≥18 years of age) patients retrospectively reported to the EBMT.
View Article and Find Full Text PDFObjective: Hemophagocytic lymphohistiocytosis is a hyperinflammatory syndrome that often requires critical care support and remains difficult to diagnose. These guidelines are meant to aid in the early recognition, diagnosis, supportive care, and treatment of patients with hemophagocytic lymphohistiocytosis in ICUs.
Data Sources: The literature searches were performed with PubMed (MEDLINE).
X-linked inhibitor of apoptosis (XIAP) deficiency is an inherited primary immunodeficiency characterized by chronic inflammasome overactivity and associated with hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease (IBD). Allogeneic hematopoietic cell transplantation (HCT) with fully myeloablative conditioning may be curative but has been associated with poor outcomes. Reports of reduced-intensity conditioning (RIC) and reduced-toxicity conditioning (RTC) regimens suggest these approaches are well tolerated, but outcomes are not well established.
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- - Patients with ataxia-telangiectasia (A-T) often experience severe issues, including progressive coordination problems, weakened immune response, and higher cancer risk, with those having IgA deficiency facing even worse outcomes.
- - A study of 659 A-T patients showed that those with IgA deficiency had significantly lower lymphocyte counts and altered immune cell types compared to those without IgA deficiency, indicating poorer health.
- - The findings suggest that IgA deficiency serves as a simple indicator of worse prognosis in A-T patients, emphasizing the need for careful monitoring and potential treatment strategies for those affected.
Background: Cytokine storm syndromes are life-threatening complications that can occur in children with rheumatic conditions (macrophage activation syndrome [MAS]), inherited cytotoxicity defects (ie, primary haemophagocytic lymphohistiocytosis [HLH]), or as a result of infection or malignancies (ie, secondary HLH). To adequately steer treatment, an early and clear discrimination of these entities is essential. We aimed to define and validate serum biomarker profiles that can differentiate between primary HLH, secondary HLH (predominantly infection-associated), and MAS associated with systemic juvenile idiopathic arthritis (systemic JIA-MAS).
View Article and Find Full Text PDFHemophagocytic lymphohistiocytosis (HLH) is a disorder of uncontrolled immune activation with distinct clinical features including fever, cytopenia, splenomegaly, and sepsis-like symptoms. In a young adolescent patient a novel germline variant (NM_032638.5 (GATA2): c.
View Article and Find Full Text PDFBackground: Rubella virus-induced granulomas have been described in patients with various inborn errors of immunity. Most defects impair T-cell immunity, suggesting a critical role of T cells in rubella elimination. However, the molecular mechanism of virus control remains elusive.
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- PAMI syndrome is a newly identified genetic disorder leading to high levels of certain proteins in the blood, causing inflammation and blood cell deficiencies, with limited response to standard therapies.
- A study involving five patients with PAMI syndrome showed that undergoing allogeneic hematopoietic stem cell transplantation (HSCT) resulted in successful engraftment and improvement of symptoms, despite some complications in two patients.
- The findings suggest that HSCT may be a promising treatment option for PAMI syndrome, offering a potential cure for related inflammatory disorders that do not respond well to other treatments.
Hemophagocytic lymphohistiocytosis (HLH) is a rare immunological disease, which can be mistaken for sepsis easily. Among the infectious causes that may trigger secondary HLH, tuberculosis (TBC), a rather rare pathogen nowadays, is typical. To our knowledge, this is the first case report of an infant suffering from TBC-associated HLH-induced acute respiratory failure who was treated successfully using extracorporeal membrane oxygenation.
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