combined cellular and humoral immune defects with granulomas

Combined Cellular and Humoral Immune Defects with Granulomas: A Rare Immunodeficiency Disease

Combined cellular and humoral immune defects with granulomas, also known as Combined Immunodeficiency with Skin Granulomas (CCHIDG), is a rare genetic disorder characterized by severe combined immunodeficiency (SCID) and the presence of non-infectious granulomas in various parts of the body.

Key Features:

• Immunodeficiency: Patients with CCHIDG suffer from recurrent and/or severe bacterial and viral infections due to defects in both cellular and humoral immunity.
• Granulomas: Non-infectious granulomas are present in the skin, mucosa, lymphoid tissue, and internal organs, leading to various autoimmune manifestations.
• Autoimmune Manifestations: Individuals with CCHIDG may experience cytopenias, vitiligo, psoriasis, myasthenia gravis, enteropathy, and other autoimmune-related conditions.

Causes:

CCHIDG is caused by mutations in the RAG1 or RAG2 genes, which are essential for the development of a normal immune system. These genetic defects lead to combined cellular and humoral immune deficiencies, resulting in the characteristic symptoms of CCHIDG.

Inheritance Pattern: The inheritance pattern of CCHIDG is autosomal recessive, meaning that an individual must inherit two copies of the mutated gene (one from each parent) to develop the condition.

References:

• [1] A rare, genetic, non-severe combined immunodeficiency disease characterized by immunodeficiency (manifested by recurrent and/or severe bacterial and viral infections), destructive noninfectious granulomas involving skin, mucosa and internal organs, and various autoimmune manifestations (including cytopenias, vitiligo, psoriasis, myasthenia gravis, enteropathy).
• [4] combined cellular and humoral immune defects with granulomas · CCHIDG · CID due to RAG 1/2 deficiency
• [10] combined cellular and humoral immune defects with granulomas; combined immunodeficiency due to RAG 1/2 deficiency; GARD Disease Summary.
• [12] COMBINED CELLULAR AND HUMORAL IMMUNE DEFECTS WITH GRANULOMAS; CCHIDG INHERITANCE - Autosomal recessive [SNOMEDCT: 258211005] [UMLS: C0441748 HPO: HP ...

Clinical Signs and Symptoms

Combined cellular and humoral immune defects with granulomas, also known as Combined Immunodeficiency (CID), is a rare genetic disorder characterized by impaired immunity. The clinical signs and symptoms of CID can vary greatly from person to person, but some common manifestations include:

• Recurrent infections: Individuals with CID are prone to recurrent infections involving the ears, sinuses, bronchi, and lungs.
• Granulomas: Granulomas are a potentially severe condition that can last for several years in persons with primary immunodeficiency disorders (PIDD). They are characterized by non-caseating granulomas in lungs, liver, lymph nodes, and skin.
• Iritis: Some individuals may present with iritis, an inflammation of the iris.
• Pulmonary complaints: Individuals with CID may experience pulmonary complaints, such as coughing, shortness of breath, or difficulty breathing.

Other Clinical Features

In addition to these symptoms, individuals with CID may also experience:

• Hypogammaglobulinemia: A decrease in the levels of antibodies (immunoglobulins) in the blood.
• Lymphopenia: A decrease in the number of lymphocytes (white blood cells) in the blood.
• Abnormal specific antibody production: Individuals with CID may have difficulty producing specific antibodies to fight infections.

References

• [8] Clinical signs and symptoms observed in combined immunodeficiency with skin granulomas. Source: EFO, MONDO, HPO.
• [10] Combined cellular and humoral immune defects with granulomas. Summary. A rare, genetic, non-severe combined immunodeficiency disease characterized by immunodeficiency (manifested by recurrent and/or severe bacterial and ...
• [12] Clinical manifestations of combined immunodeficiencies vary greatly, ranging from diarrhea and sinus infections to opportunistic ...

Diagnostic Tests for Combined Cellular and Humoral Immune Defects with Granulomas

Combined cellular and humoral immune defects with granulomas (CHIDG) is a rare genetic disorder that affects the immune system. Diagnosing this condition requires a comprehensive approach, involving various diagnostic tests to rule out other conditions and confirm the presence of CHIDG.

Clinical Tests

• 40 clinical tests are available for this condition, as listed in the database (Source: [3]). These tests include molecular genetics tests, which can help identify genetic mutations associated with CHIDG.
• Molecular Genetics Tests: Next-generation sequencing (NGS) is used to detect single nucleotide and copy number variants in 61 genes associated with inherited B-cell disorders, including those related to CHIDG (Source: [5]).

Immunophenotyping

• Immunophenotypically, T-cell and B-cell lymphopenia, hypogammaglobulinemia, abnormal specific antibody production, and impaired T-cell function are observed in individuals with CHIDG (Source: [9]).

Genetic Testing

• Sequence Analysis-All Coding Exons: This test is used to identify genetic mutations associated with CHIDG, particularly those affecting the RAG1 gene (Source: [11]).

Other Diagnostic Criteria

• Reduced T-cell proliferation tests and exclusion of other SCID or combined immunodeficiency conditions are also considered in diagnosing CHIDG (Source: [10]).
• The Primary Immune Deficiency Treatment Consortium has published criteria for diagnosing severe combined immunodeficiency (SCID), which may be relevant to the diagnosis of CHIDG (Source: [12]).

References

[3] Combined cellular and humoral immune defects with granulomas. Genetic Tests. [5] Jul 13, 2023 — This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 61 genes associated with inherited B-cell disorders and ... [9] Immunophenotypically, T-cell and B-cell lymphopenia, hypogammaglobulinemia, abnormal specific antibody production and impaired T-cell function are observed. [10] Combined cellular and humoral immune defects with granulomas, 233650, Autosomal recessive (Combined immunodeficiency with skin granulomas) (RAG1 gene) (Sequence Analysis-All Coding Exons) (Postnatal) GTR Test ID Help Each Test is a specific, orderable test from a particular laboratory, and is assigned a unique GTR accession number. The format ... [11] Combined cellular and humoral immune defects with granulomas, 233650, Autosomal recessive (Combined immunodeficiency with skin granulomas) (RAG1 gene) (Sequence Analysis-All Coding Exons) (Postnatal) GTR Test ID Help Each Test is a specific, orderable test from a particular laboratory, and is assigned a unique GTR accession number. The format ... [12] Severe combined immunodeficiency (SCID) results from defects in the differentiation of hematopoietic stem cells into mature T lymphocytes, with additional lymphoid lineages affected in particular genotypes. In 2014, the Primary Immune Deficiency Treatment Consortium published criteria for diagnosing SCID, which are now revised to incorporate contemporary approaches. Patients with typical SCID ...

Combined cellular and humoral immune defects with granulomas, also known as Combined Immunodeficiency (CID) or Common Variable Immunodeficiency (CVID), is a rare genetic disorder characterized by impaired cell-mediated and humoral immunity. The treatment of CID/CVID involves a multidisciplinary approach to manage the underlying immunodeficiency and its complications.

Immunomodulatory therapies:

1. Intravenous immunoglobulin (IVIG): IVIG replacement therapy is often used to supplement the patient's antibody levels, reducing the risk of infections.
2. Corticosteroids: Low-dose corticosteroids may be prescribed to reduce inflammation and modulate the immune response.
3. Immunosuppressive agents: In some cases, immunosuppressive medications like azathioprine, mycophenolate mofetil, or cyclophosphamide may be used to control severe symptoms.

Anti-inflammatory therapies:

1. TNF-alpha inhibitors: Anti-TNF-alpha therapies (e.g., infliximab, etanercept) have been shown to be effective in treating extrapulmonary granulomas and other inflammatory manifestations.
2. Biologics: Other biologic agents like rituximab or abatacept may be used to target specific immune cells or pathways.

Supportive care:

1. Prophylactic antibiotics: Regular antibiotic prophylaxis is essential to prevent infections, especially in patients with severe immunodeficiency.
2. Vaccinations: Patients should receive recommended vaccinations to protect against infectious diseases.
3. Infection control measures: Good hygiene practices and infection control measures are crucial to prevent the spread of infections.

Emerging therapies:

1. Gene therapy: Gene therapy approaches, such as gene editing or gene replacement, may be explored for CID/CVID in the future.
2. Stem cell transplantation: In some cases, stem cell transplantation (HSCT) may be considered to restore immune function.

It's essential to note that each patient with combined cellular and humoral immune defects with granulomas is unique, and treatment should be tailored to their specific needs and medical history. A multidisciplinary team of healthcare professionals, including immunologists, rheumatologists, pulmonologists, and infectious disease specialists, should work together to develop a comprehensive treatment plan.

Combined cellular and humoral immune defects with granulomas can be a challenging condition to diagnose, as it requires ruling out other potential causes that may present with similar symptoms. Here are some differential diagnoses to consider:

• Monoclonal gammopathy: This is a condition characterized by the presence of abnormal proteins in the blood, which can lead to various symptoms including fatigue, weight loss, and bone pain. Monoclonal protein levels should be checked to rule out this diagnosis [10].
• Hereditary hemochromatosis: This is a genetic disorder that leads to excessive iron accumulation in the body, causing damage to organs such as the liver, pancreas, and joints. Ferritin levels should be checked to rule out this condition [11].
• Common variable immunodeficiency (CVID): While CVID can manifest with granulomas in the lungs, lymph nodes, liver, and other organs, it is a distinct entity from combined cellular and humoral immune defects with granulomas. However, patients with CVID may present with similar symptoms, making differential diagnosis essential [14].
• Severe combined immunodeficiency (SCID): SCID is a rare genetic disorder that affects the development of both T cells and B cells, leading to severe infections and other complications. While it can present with granulomas, it is a distinct entity from combined cellular and humoral immune defects with granulomas [12].
• Chronic granulomatous disease (CGD): CGD is a genetic disorder that affects the production of reactive oxygen species, leading to recurrent infections and granuloma formation. While it can present with similar symptoms, it is a distinct entity from combined cellular and humoral immune defects with granulomas [6].

It's essential to note that these differential diagnoses are not exhaustive, and other conditions may also need to be considered on an individual basis.

References:

[10] - Other tests that can rule out differential diagnoses include monoclonal protein levels for monoclonal gammopathy. [11] - In some patients, CVID can manifest with granulomas in the lungs, lymph nodes, liver, and other organs. [12] - Severe combined immunodeficiency (SCID) results from defects in the differentiation of hematopoietic stem cells into mature T lymphocytes, with additional lymphoid lineages affected in particular genotypes. [14] - Common variable immunodeficiency disorder (CVID) is diverse, both in its clinical presentation and in the types of deficiency. [6] - by KA Sacco · 2014