Adult-onset immunodeficiency syndrome

Overview

Adult-Onset Immunodeficiency Syndrome is a rare acquired immune disorder characterized by the body’s inability to fight off infections, particularly opportunistic infections typically seen in individuals with severe immune suppression. Unlike congenital immunodeficiencies or HIV-related immunosuppression, this condition develops spontaneously in adulthood, often without any prior health issues. A defining feature of this syndrome is the presence of autoantibodies against interferon-gamma (IFN-γ), a key cytokine involved in defending the body against intracellular pathogens.

Causes

The primary cause of adult-onset immunodeficiency syndrome is the development of neutralizing autoantibodies against interferon-gamma (anti–IFN-γ autoantibodies). These antibodies block the action of IFN-γ, impairing the immune system’s ability to activate macrophages and other immune responses against intracellular bacteria, fungi, and viruses.

Although the exact cause of autoantibody development is unknown, the condition has been most frequently reported in people of Southeast Asian descent, suggesting a possible genetic or environmental predisposition.

Symptoms

Symptoms often resemble those seen in advanced immunodeficiency states. They are usually caused by recurrent or persistent infections and may include:

• Fever and night sweats

• Weight loss and fatigue

• Enlarged lymph nodes (lymphadenopathy)

• Chronic cough or respiratory infections

• Bone, joint, or skin lesions

• Recurrent or disseminated nontuberculous mycobacterial (NTM) infections

• Infections with Salmonella, histoplasmosis, cryptococcosis, or varicella-zoster virus (VZV)

The disease can progress slowly, and patients often have multiple infections that are difficult to treat or recur after therapy.

Diagnosis

Diagnosis involves a detailed clinical assessment, laboratory testing, and exclusion of other immunodeficiencies such as HIV. Steps include:

• Infectious disease workup: Identification of unusual or recurrent intracellular infections

• HIV testing: To rule out HIV/AIDS

• Immunologic assays: Blood tests showing impaired T-cell function despite normal CD4 counts

• Detection of anti–IFN-γ autoantibodies: Confirmed through specialized immunoassays

• Imaging studies: To evaluate lymphadenopathy, lung lesions, or disseminated infection

Diagnosis is often delayed due to the non-specific nature of symptoms and the rarity of the condition.

Treatment

Treatment focuses on two primary goals: managing infections and suppressing the production of autoantibodies. Therapeutic strategies include:

1. Antimicrobial Therapy:

• Long-term antibiotic or antifungal treatment tailored to the specific pathogen (e.g., macrolides for NTM)

• Monitoring for recurrence or reinfection

2. Immunosuppressive or Immunomodulatory Therapy:

• Rituximab: A monoclonal antibody used to reduce B-cell production of autoantibodies

• Cyclophosphamide or corticosteroids: Occasionally used in resistant or severe cases

3. Supportive Care:

• Nutritional support

• Regular infectious disease follow-up

• Avoidance of live vaccines

Prognosis

The prognosis of adult-onset immunodeficiency syndrome varies depending on the severity of infections, response to treatment, and access to care. Early diagnosis and appropriate antimicrobial and immunomodulatory therapy can significantly improve outcomes. However, due to the chronic and relapsing nature of infections and immune dysfunction, many patients require lifelong monitoring and treatment.

With advances in understanding and treatment, including the use of targeted therapies like rituximab, long-term survival and quality of life are improving, especially when care is managed by an experienced multidisciplinary team.