Pathology Notes

Common Variable Immunodeficiency   Updated: 08/17/2020 © Jun Wang, MD, PhD General features Heterogeneous group with no clearly understood etiology Hereditary or sporadic No recognizable inheritance pattern High risk of autoimmune, inflammatory and malignant disorders Increased risk of gastric carcinoma, melanoma and EB virus associated B cell lymphoma Diagnosis of exclusion Clinical presentations 5 distinct clinical phenotypes No complications Antoimmunity Polyclonal lymphocytic infiltrate Enteropathy Lymphoid malignancy Recurrent infections including diarrhea, pneumonia, otitis media, sinusitis etc Splenomegaly and generalized lymphadenopathy Autoimmune disorders Skin manifestations: Alopecia, etc Genetic abnormalities Variable Transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) Inducible co-stimulator of activated T cells (ICOS) Others Pathogenesis Defects in immunoglobulin production due to either in

DiGeorge syndrome Updated: 08/17/2020 © Jun Wang, MD, PhD General features Inherited or sporadic Multiple organ/tissue defects Complete (absence) or partial (underdeveloped) thymus Congenital heart disease most common cause of death Clinical presentations Facial appearance: Elongated face , retrognathia or micrognathia, cleft palate etc Congenital heart defects Neonatal hypocalcemia T-cell dysfunction, although infections are not the first manifestation Recurrent infections associated with T cell dysfunction: fungal, Pneumocystis jiroveci, viral, etc Genetic abnormality Deletion of 22q11.2 Pathogenesis Failure of 3 rd and 4 th pharyngeal pouches Heart involvement: Congenital heart diseases Parathyroid defects: hypocalcemia Thymus defect: No or deficient T-cell proliferation in response to mitogen Key Laboratory findings Reduced levels of T cells in peripheral blood Hypocalcemia Genetic studies (FISH) for 22q11.2 Key morphological feature

Ataxia telangiectasia Updated: 08/17/2020 © Jun Wang, MD, PhD General features Autosomal recessive Clinical presentations Progressive impairment of neurological deficits, vascular malformation and immunodeficiency affecting both B and T cells Recurrent sinopulmonary infections Development defects Genetic abnormality Mutation of ATM Pathogenesis Defected DNA repair, abnormal function of p53 Laboratory findings Thrombocytopenia Platelet dysfunction Managements Treat infections Treat correlated abnormalities Back to primary immunodeficiency disorders Back to contents

X-linked agammaglobulinemia Updated: 08/17/2020 © Jun Wang, MD, PhD General features AKA Bruton's disease Impaired B cell differentiation and immunoglobulin production X-linked Almost exclusively in boys Clinical presentations Recurrent infections, especially encapsulated pyogenic bacteria, such as Streptococcus Pneumoniae Commonly pneumonia, otitis media, diarrhea, etc Presentations starts 4-6 months after birth Genetic abnormality Bruton tyrosine kinase mutation Pathogenesis B cell development arrest Key Laboratory findings Low levels of Ig after 6 months, IgM and IgA typically undetectable Markedly reduced or absent CD19+ B cells in circulation Circulating T cells may be increased Key morphological features Underdeveloped or absent lymphoid tissue, such as lymph nodes, tonsils, etc. Absent plasma cells Diagnosis Low or absent number of mature B cells Low or absent expression of m heavy chain on surface of lymphocytes Molecular t

Severe combined immunodeficiency   Updated: 07/19/2022 © Jun Wang, MD, PhD General features Heterogeneous group Variable genetic abnormalities T-cell defects with associated B-cell dysfunction May develop non-Hodgkin lymphoma Death may occur within first year of life unless stem cell transplantation Clinical presentations Usually have positive family history Presentation shortly after birth Severe and often life threatening infections Opportunistic infections Failure to thrive Mucocutaneous candidiasis resistant to treatment Autoimmune disorders Genetic abnormalities and associated pathogenesis X-linked : most common type, mutations of common gamma-chain of interleukin receptors , causing defective lymphocytic proliferative (IL-2), B-cell class switch (IL-4), T-cell selection in thymus (IL-7), and NK-cell development (IL-15) Autosomal recessive : mutation of adenosine deaminase , etc, causing accumulation of cytotoxic DNA byproducts (Deoxy-ATP, etc) and s

Primary immunodeficiency disorders   Updated: 07/14/2023 © Jun Wang, MD, PhD General features Preferred term: Inborn errors of immunity   Deficiency in immune system function due to intrinsic defects Poor or absent function of one or more components of the immune system Rare condition except IgA deficiency Early diagnosis and treatment critical for outcomes Clinical presentations Recurrent infections Opportunistic infections Unusual infections Autoimmune disorders Key Laboratory findings Lymphocytopenia Neutropenia Abnormal levels of immunoglobulin Screening tests: immunodeficiency unlikely if normal results CBC and differential: neutrophils, lymphocytes Quantitative serum immunoglobulin levels IgA, IgE, IgG and IgM Levels of specific antibodies to vaccines Skin testing for delayed hypersensitivity Additional tests Lymphocytopenia : Flow cytometry/immunophenotyping, antibodies to T, B or NK cells Cellular immunity dysfunction : T-cell receptor e