• Mycobacterium avium complex
• Case report
• Meningitis
• Non-HIV
• Non-tuberculous mycobacterial meningitis

• Humans
• Male
• Middle Aged
• Fatal Outcome
• Vietnam
• Mycobacterium avium-intracellulare Infection/drug therapy
• Mycobacterium avium-intracellulare Infection/diagnosis
• Mycobacterium avium-intracellulare Infection/complications
• Mycobacterium avium Complex/isolation & purification
• Magnetic Resonance Imaging
• Anti-Bacterial Agents/therapeutic use
• Meningitis, Bacterial/drug therapy
• Meningitis, Bacterial/diagnosis
• Meningitis, Bacterial/microbiology
• Meningitis, Bacterial/complications
• Cerebral Hemorrhage/diagnostic imaging
• Cerebral Hemorrhage/microbiology
• HIV Seronegativity
• Southeast Asian People

• 206724/Z/17/Z Wellcome Trust Fellowship in Public Health and Tropical Medicine and Wellcome Trust to Vietnam Africa Asia Programme

• anti-GM-CSF
• anti-interferon
• anti-interleukin
• cryptococcus
• cytokine
• non-tuberculous mycobacteria
• secondary immunodeficiency

• Humans
• Autoantibodies
• Autoimmunity
• Cytokines
• Immunomodulation
• Communicable Diseases

Several reports of adult-onset immunodeficiency syndrome have been associated with anti-interferon-gamma (IFN-γ) autoantibodies (AIGAs). However, it is rare to find AIGAs with intracranial infections.

In this case study, we report a case of an AIGAs with intracranial infection and hand rashes considered Sweet’s syndrome. The patient presented to our hospital with a persistent cough, a fever that had been going on for 6 mo, and a rash that had been going on for a week. The patient started losing consciousness gradually on the fourth day after admission, with neck stiffness and weakened limb muscles. The upper lobe of the left lung had a high-density mass with no atypia and a few inflammatory cells in the interstitium. Brain magnetic resonance imaging and cerebrospinal fluid suggest intracranial infection. The pathology of the skin damage on the right upper extremity revealed an infectious lesion that was susceptible to Sweet’s disease. It has an anti-IFN-γ autoantibody titer of 1:2500. She was given empirical anti-non-tuberculous mycobacterial and antifungal treatments. The patient had no fever, obvious cough, headache, or rash on the hand. She got out of bed and took care of herself following hospitalization and discharge with medicine.

Adults with severe and recurrent infections of several organs should be considered for AIGAs if no other known risk factors exist. AIGAs are susceptible to subsequent intracranial infections and Sweet’s syndrome.

• Adult-onset immunodeficiency syndrome
• Anti-interferon-gamma autoantibodies
• Intracranial infection
• Sweet disease
• Case report

• Interferon-γ
• SARS-CoV-2
• anti-Interferon antibody
• cord blood
• immune system
• pregnancy

• anti-IFN-γ autoantibody
• epidemiology
• immunodeficiency
• immunotherapy
• immunotherapy pathogen spectrum

• disseminated Mycobacterium avium complex infection
• epidural intracranial abscess
• interferon-ɤ neutralization antibody

• AOID
• AOIS
• Adult onset immunodeficiency
• Anti-interferon-gamma autoantibody
• Disseminated MAC
• IgG4
• IgG4-related disease IgG4-RD

• Burkholderia
• Chronic granulomatous disease
• DHR assay
• PKCδ

• Mycobacterium kansasii
• POEMS syndrome
• TAFRO syndrome
• anti-interferon-γ antibody
• disseminated nontuberculous mycobacterial infection

• Autoantibodies
• Castleman Disease
• Humans
• Interferon-gamma
• Mycobacterium Infections, Nontuberculous/diagnosis
• Mycobacterium Infections, Nontuberculous/drug therapy
• Opportunistic Infections

Adult-onset immunodeficiency syndrome (AOID) patients with autoantibodies (autoAbs) against interferon-gamma (IFN-γ) generally suffer from recurrent and recalcitrant disseminated non-tuberculous mycobacterial diseases. Since the early stages of AOID do not present specific symptoms, diagnosis and treatment of the condition are not practical. A simplified diagnostic method for differentiating AOID from other immunodeficiencies, such as HIV infection, was created. Anti-IFN-γ is generally identified using enzyme-linked immunosorbent assay (ELISA), which involves an instrument and a cumbersome process. Recombinant IFN-γ indirectly conjugated to colloidal gold was used in the modified immunochromatographic (IC) strips. The biotinylated-IFN-γ was incorporated with colloidal-gold-labeled 6HIS-maltose binding protein-monomeric streptavidin (^6HISMBP-mSA) and absorbed at the conjugate pad. The efficacy of the IC strip upon applying an anti-IFN-γ autoAb cut-off ELISA titer of 2500, the sensitivity and specificity were 84% and 90.24%, respectively. When a cut-off ELISA titer of 500 was applied, the sensitivity and specificity were 73.52% and 100%, respectively.

• anti-interferon-γ autoantibody
• conventional indirect ELISA
• immunochromatographic strip test
• interferon-γ

Non-tuberculous mycobacteria (NTM) is a collective name given to a group of more than 190 species of Mycobacterium. The clinical presentation for most NTM infections is non-specific, often resulting in delayed diagnosis. Further complicating matters is that NTM organisms can be difficult to isolate. Medications used to treat NTM infection can be difficult for patients to tolerate, and prolonged courses of anti-mycobacterial therapy are often required for adequate suppression or eradication. Herein, we review different NTM syndromes, appropriate diagnostic tests, and treatment regimens.

• ADR, adverse drug reactions
• AFB, acid fast bacilli
• AST, antimicrobial-susceptibility testing
• ATS, American Thoracic Society
• BCG, Bacille Calmette-Guerin
• CLSI, Clinical and Laboratory Standards Institute
• COPD, chronic obstructive pulmonary disease
• ECG, electrocardiogram
• EMB, ethambutol
• Erm, erythromycin ribosomal methylase
• FDA, Food and Drug Administration
• HIV, human immunodeficiency virus
• HRCT, high resolution computed tomography
• IDSA, Infectious Disease Society of America
• INF-γ, interferon- γ
• INH, isoniazid
• MAC, Mycobacterium avium complex
• MALDI-TOF, matrix-assisted laser desorption ionization time-of-flight mass spectrometry
• MGIT, mycobacteria growth indicator tube
• MIC, minimum inhibitory concentrations
• Mycobacterium abscessus
• Mycobacterium avium
• NTM, non-tuberculous mycobacteria
• Non-tuberculous mycobacteria
• PCR, polymerase chain reaction
• PFT, pulmonary function test
• TB, tuberculosis
• TDM, therapeutic drug monitoring

• adult-onset immunodeficiency
• anti-interferon-γ autoantibodies
• anticytokine autoantibodies
• disseminated nontuberculous mycobacterial infection
• opportunistic infection

• Immune deficiency
• adult-onset immunodeficiency
• anti-interferon-γ antibodies
• intracellular organism infection

• IFN-γAb
• chylous ascites
• disseminated nontuberculous mycobacteriosis

• Aged
• Autoantibodies
• Chylous Ascites/etiology
• Humans
• Interferon-gamma
• Male
• Mycobacterium avium
• Mycobacterium avium Complex
• Mycobacterium avium-intracellulare Infection/complications
• Mycobacterium avium-intracellulare Infection/drug therapy

• anti–interferon-gamma autoantibody
• non-tuberculous mycobacterial infection
• reactive dermatosis

• Aged
• Autoantibodies/immunology
• Humans
• Immunologic Deficiency Syndromes/complications
• Immunologic Deficiency Syndromes/diagnosis
• Immunologic Deficiency Syndromes/immunology
• Interferon-gamma/immunology
• Male
• Mycobacterium Infections, Nontuberculous/complications
• Mycobacterium Infections, Nontuberculous/diagnosis
• Mycobacterium Infections, Nontuberculous/immunology
• Opportunistic Infections/complications
• Skin Diseases/complications
• Skin Diseases/immunology

Mycobacterial species other than Mycobacterium tuberculosis and Mycobacterium leprae are generally free-living organisms and Mycobacterium simiae is one of the slowest growing Non-tuberculous mycobacteria. This is the first case report of Mycobacterium simiae infection in Sri Lanka and only very few cases with extrapulmonary manifestation reported in the literature.

A 24-year-old, previously healthy Sri Lankan male presented with generalized lymphadenopathy with discharging sinuses, evening pyrexia, weight loss, poor appetite and splenomegaly. Lymph node biopsies showed sheets of macrophages packed with organisms in the absence of granulomata. Ziehl Neelsen, Wade Fite and Giemsa stains revealed numerous red coloured acid-fast bacilli within foamy histiocytes. Slit skin smear for leprosy was negative and tuberculosis, fungal and bacterial cultures of the lymph node and bone marrow did not reveal any growth. Later he developed watery diarrhea and colonoscopy revealed multiple small polyps and ulcers throughout the colon extending up to the ileum, Which was confirmed to be due to cytomegalovirus confirmed by PCR and successfully treated with ganciclovir. Positron emission tomography scan guided biopsies of the gut and lymph nodes confirmed presence of mycobacterial spindle cell pseudo-tumours and PCR assays revealed positive HSP65. The culture grew Mycobacterium Simiae. Flow cytometry analysis on patient’s blood showed extremely low T and B cell counts and immunofixation revealed low immunoglobulin levels. His condition was later diagnosed as adult onset immunodeficiency due to anti- interferon – gamma autoantibodies. He was initially commenced on empirical anti-TB treatment with atypical mycobacterial coverage. He is currently on a combination of daily clarithromycin, ciprofloxacin, linezolid with monthly 2 g/kg/intravenous immunoglobulin to which, he had a remarkable clinical response with complete resolution of lymphadenopathy and healing of sinuses.

This infection is considered to be restricted to certain geographic areas such as mainly Iran, Cuba, Israel and Arizona and this is the first case report from Sri lanka. Even though the infection is mostly seen in the elderly patients, our patient was only 24 years old. In the literature pulmonary involvement was common presentation, but in this case the patient had generalized lymphadenopathy and colonic involvement without pulmonary involvement.

• Adult-onset immunodeficiency due to anti-interferon-gamma antibodies
• Case report
• Disseminated Mycobacterium simiae infection
• Sri lanka

The most common infection in patients positive for anti-interferon-gamma autoantibodies (anti-IFN-γ AAbs) is disseminated nontuberculous mycobacterial (dNTM) infection. Here, we report a rare case of triple infection caused by Cryptococcus, varicella-zoster virus (VZV), and nontuberculous mycobacterium in a patient with anti-IFN-γ AAbs.

A 53-year-old Thai man presented with a progressively enlarging right cervical mass with low-grade fever and significant weight loss for 4 months. He also developed a lesion at his left index finger. A biopsy of that lesion showed granulomatous inflammation with yeast-like organisms morphologically consistent with cryptococcosis. Serum cryptococcal antigen was positive. Histopathology of a right cervical lymph node revealed chronic granulomatous lymphadenitis, and the lymph node culture grew Mycobacterium abscessus. One month later, he complained of vision loss in his left eye and subsequently developed a group of painful vesicles at the right popliteal area of S1 dermatome. Lumbar puncture was performed and his cerebrospinal fluid was positive for VZV DNA. His blood test for anti-HIV antibody was negative. Anti-IFN-γ AAbs was positive, but test for anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF AAbs) was negative. He was treated with amphotericin B plus fluconazole for cryptococcosis; a combination of amikacin, imipenem, azithromycin, and levofloxacin for dNTM infection; and, intravenous acyclovir for disseminated VZV infection. After treatment, our patient’s fever and cervical lymphadenopathy were subsided, and his vision and visual acuity were both improved.

This is the first case of triple infection with cryptococcosis, VZV, and dNTM in a patient who tested positive for anti-IFN-γ AAbs and negative for anti-GM-CSF AAbs. This case will increase awareness and heighten suspicion of these infections in patients with the described presentations and clinical characteristics, and this will accelerate diagnosis and treatment.

• Anti-interferon-gamma autoantibody
• Cryptococcus
• Mycobacterium abscessus
• Nontuberculous mycobacteria
• Varicella-zoster virus

• granuloma
• injectable
• mycobacterium abscessus
• mycobacterium haemophilum
• surgery

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antifungal Agents/therapeutic use
• Child
• Child, Preschool
• Female
• Humans
• Male
• Middle Aged
• Mycobacterium Infections, Nontuberculous/diagnosis
• Mycobacterium Infections, Nontuberculous/epidemiology
• Nontuberculous Mycobacteria/drug effects
• Nontuberculous Mycobacteria/pathogenicity
• Odds Ratio
• Prevalence
• Retrospective Studies
• Thailand/epidemiology

• Anti-interferon gamma antibody
• ELISA
• Interferon gamma
• Natural autoantibodies
• Varicella

• Antibodies/adverse effects
• Antibodies/therapeutic use
• Antiviral Agents/adverse effects
• Antiviral Agents/therapeutic use
• Autoantibodies/immunology
• Autoantigens/immunology
• Case-Control Studies
• Chickenpox/drug therapy
• Chickenpox/immunology
• Chickenpox/virology
• Child
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Interferon-gamma/immunology
• Male
• Pilot Projects

Patients with high-titer anti-IFN-γ autoantibodies present disseminated non-tuberculous mycobacterial (NTM) and other opportunistic infections. Due to its rare occurrence and non-specific symptoms, this syndrome is difficult to diagnose during early disease stages. Here, we report a case with high-concentrations of serum anti-IFN-γ autoantibodies who presented with disseminated Talaromyces marneffei and NTM disease accompanied Sweet’s syndrome.

A 62-year-old Chinese woman with no previous history was admitted to our hospital in August 2016 due to intermittent fever for 2 years, left chest wall redness, and swelling for 3 months. During hospitalization, the patient was confirmed with disseminated T. marneffei and successfully treated with antifungal therapy. In July 2017, upon second admission, Mycobacterium avium intracellular (MAC) pulmonary infection was established after positive cultures from the right lung tissue. The patient failed treatment after 1 month of anti-NTM therapy due to side effects. In May 2018, she was confirmed as having disseminated MAC disease accompanied by hand rashes, which was considered as Sweet’s syndrome. High-level anti-IFN-γ antibodies in the patient serum were detected upon comparison with normal controls (2.85-fold increase). Following anti-NTM therapy, both symptoms and pulmonary infiltration gradually improved, and joint destruction and lymphadenitis remained.

Patients with anti-interferon-γ autoantibodies should be considered for severe, recurrent infections in adults in the absence of other known risk factors. Sweet’s syndrome is a common skin manifestation of the syndrome.

• Mycobacterium avium
• Sweet’s syndrome
• Talaromyces marneffei
• autoantibodies
• interferon-gamma

Autoantibodies to cytokines are increasingly being detected in association with immunodeficient, autoimmune and immune dysregulated states. Presence of these autoantibodies in an otherwise healthy individual may result in a unique phenotype characterized by predisposition to infection with specific organisms. The ability to detect these autoantibodies is of importance as it may direct treatment toward a combination of anti-microbial agents and immunomodulatory therapies that decrease autoantibody levels, thereby releasing the immune system from autoantibody-mediated inhibition. Ligand binding assays such as ELISA or bead multiplex assays have been used to detect these antibodies. However, not all anti-cytokine autoantibodies have demonstrable function in vitro and therefore their clinical significance is unclear. Assays that evaluate the functionality of anti-cytokine autoantibodies can supplement such ligand binding assays and add valuable functional information that, when viewed in the context of the clinical phenotype, may guide the use of adjunctive immunomodulatory therapy. This mini review provides an overview of anti-cytokine autoantibodies identified to date and their clinical associations. It also describes the use of flow cytometry for the functional analysis of anti-IFNγ and anti-GM-CSF autoantibodies.

• GM-CSF
• autoantibodies
• cytokines
• flow cytometry
• interferon gamma
• non-tuberculous mycobacteria
• phosphorylation

• Anti-interferon-gamma autoantibodies
• immunodeficiency
• non-tuberculous mycobacteria

Clinical courses and treatment outcomes are largely unknown in patients with adult-onset immunodeficiency associated with anti-interferon-gamma autoantibodies due to the fact that it was recently recognized and anti-IFN-γ auto-Abs detection is not widely available.

Non-HIV-infected adult patients with detectable anti-IFN-γ auto-Abs diagnosed and followed at Siriraj Hospital, Bangkok, Thailand during January 2013 to November 2016 were prospectively studied. At each follow-up visit, patients were classified as stable or active disease according to symptoms and signs, and all proven OIs were recorded. Laboratory parameters, including erythrocyte sedimentation rate, C-reactive protein, and anti-IFN-γ auto-Abs level, were compared between active and stable disease episodes. We identified 80 patients with this clinical syndrome and followed them up during study period. Seventy-nine patients developed overall 194 proven opportunistic infections. Mycobacterium abscessus (34.5%) and Salmonella spp. (23.2%) were the two most common pathogens identified among these patients. Sixty-three patients were followed for a median of 2.7 years (range 0.6–4.8 years). Eleven (17.5%) patients achieved the drug-free remission period for at least 9 months. Four patients died. Anti-IFN-γ auto-Abs concentration was significantly lower at baseline and decreased over time in the drug-free remission group compared to another group (p = 0.001). C-reactive protein, erythrocyte sedimentation rate and white cell count were found to be useful biomarkers for determining disease activity during follow-up.

Reinfection or relapse of OIs is common despite long-term antimicrobial treatment in patients with anti-IFN-γ auto-Abs. Treatment to modify anti-IFN-γ auto-Abs production may improve long-term outcomes in this patient population.

• Adult
• Aged
• Autoantibodies/blood
• Autoantibodies/immunology
• Biomarkers/blood
• Blood Sedimentation
• C-Reactive Protein/analysis
• Female
• Follow-Up Studies
• Humans
• Immunologic Deficiency Syndromes/complications
• Immunologic Deficiency Syndromes/diagnosis
• Immunologic Deficiency Syndromes/immunology
• Interferon-gamma/immunology
• Lymphocyte Count
• Male
• Middle Aged
• Mycobacterium Infections, Nontuberculous/complications
• Mycobacterium Infections, Nontuberculous/diagnosis
• Mycobacterium Infections, Nontuberculous/immunology
• Opportunistic Infections/complications
• Opportunistic Infections/diagnosis
• Opportunistic Infections/immunology
• Prospective Studies
• Recurrence
• Salmonella Infections/complications
• Salmonella Infections/diagnosis
• Salmonella Infections/immunology
• Thailand
• Young Adult

Anti-interferon-gamma (IFN-γ) autoantibodies are increasingly recognized as a cause of adult-onset immunodeficiency (AOID) worldwide. These patients are susceptible to various intracellular pathogens especially nontuberculous mycobacteria. Most of the patients have a refractory clinical course. Herein, we report the use of immunotherapy with pulse intravenous cyclophosphamide (IVCY) in patients who had progressive, refractory Mycobacterium abscessus infection.

We included patients, seen at Srinagarind Hospital, Thailand, infected with M. abscessus, who had received ≥3 courses of parenteral antibiotics within the last 12 months and who received pulse IVCY with a tapering dose of prednisolone.

There were 8 AOID patients who met the criteria and received pulse IVCY between January 2011 and December 2015. One patient was lost to follow-up after 5 courses of IVCY: he had died at home 3 months later. Five patients had favorable outcomes: 2 were able to discontinue NTM therapy, and 3 had stable disease and were on NTM treatment without hospitalization for parenteral antibiotics. Two patients relapsed and needed hospitalization. The IFN-γ Ab titers among the 7 patients were significantly decreased during treatment, and the median initial antibody titer started at 200,000 and then decreased to 5,000 after 2 years of treatment (P < 0.0001). The antibody titer reduction among responsive vs. nonresponsive patient was significantly different after 6 months of treatment: the median antibody titer was 5,000 and 100,000, respectively (P = 0.0467).

IVCY therapy might be an alternative treatment for AOID patients infected with M. abscessus and refractory to antimycobacterial therapy.

Nontuberculous mycobacterial (NTM) infection is increasing worldwide. Current epidemiological data and knowledge of risk factors for this disease are limited. We investigated the trends in and risk of NTM infection in Northeast Thailand during 2012–2016.

Patient demographics, infection site(s), and underlying disease or conditions from 530 suspected cases of NTM infections were retrieved from medical records, reviewed and analyzed. A diagnosis of true NTM infection was accepted in 150 cases. Risk factor analyses were done for extrapulmonary NTM infections compared to pulmonary NTM infections and for Mycobacterium abscessus compared to members of the Mycobacterium avium complex (MAC). Trend analysis among NTM species causing NTM infections was performed.

The most common species of NTMs causing extrapulmonary (n = 114) and pulmonary (n = 36) NTM infections in Northeast Thailand were M. abscessus (25.4% of extrapulmonary infected cases and 27.8% of pulmonary cases) followed by MAC (14.9% of extrapulmonary and 13.9% of pulmonary cases). Presence of anti-IFN-γ autoantibodies was the major risk factor for extrapulmonary (odds ratio (OR) = 20.75, 95%CI [2.70–159.24]) compared to pulmonary NTM infection. M. abscessus infection was less likely (OR = 0.17; 95%CI [0.04–0.80]) to be found in patients with HIV infection than was MAC infection. The prevalence of NTM infection, especially M. abscessus, in Northeast Thailand has recently increased. Extrapulmonary NTM and complicated NTM infections have increased in concordance with the recent trend of increasing frequency of anti-IFN-γ autoantibodies in the population.

M. abscessus was the commonest NTM pathogen followed by MAC. The prevalence of NTM infections and anti-IFN-γ are showing an upward trend. Autoimmune disease due to anti-IFN-γ is the major risk factor for extrapulmonary NTM infection in Northeast Thailand.

• Anti-IFN-γ
• Extrapulmonary NTM infection
• IFN-γ autoantibodies
• Mycobacterium abscessus
• Mycobacterium avium complex
• Nontuberculous mycobacteria

• Herpesviridae
• Interleukine 12
• Laos
• Mycobacterium
• Nontuberculous mycobacteria
• antibody
• antimycobacteria
• autoantibodies
• avium
• bacteria
• fortuitum
• immunodeficiency
• interferon-gamma
• interferon-γ
• intracellulare
• monoclonal
• non-tuberculous
• tuberculosis and other mycobacteria

• Anti-Bacterial Agents/therapeutic use
• Autoantibodies/immunology
• Disease Susceptibility
• Drug Therapy, Combination
• Female
• Humans
• Interferon-gamma/immunology
• Middle Aged
• Mycobacterium Infections, Nontuberculous/diagnosis
• Mycobacterium Infections, Nontuberculous/drug therapy
• Mycobacterium Infections, Nontuberculous/immunology
• Mycobacterium Infections, Nontuberculous/microbiology
• Nontuberculous Mycobacteria/immunology
• Treatment Outcome

• Cutaneous lesions
• Disseminated Mycobacterium kansasii infection

• Adult-onset immunodeficiency
• Anti-interferon-gamma autoantibody
• Clinical manifestation
• Ethnicity
• Nontuberculous mycobacterium

• Autoantibodies/immunology
• Humans
• Interferon-gamma/immunology
• Mycobacterium Infections, Nontuberculous/immunology
• Nontuberculous Mycobacteria/immunology

• autoantibody
• interferon-gamma
• nontuberculous mycobacterium
• taiwan

• Adult
• Aged
• Aged, 80 and over
• Anti-Bacterial Agents/therapeutic use
• Antibodies, Anti-Idiotypic/immunology
• Autoantibodies/immunology
• Female
• Follow-Up Studies
• Humans
• Incidence
• Interferon-gamma/immunology
• Male
• Middle Aged
• Mycobacterium Infections, Nontuberculous/drug therapy
• Mycobacterium Infections, Nontuberculous/epidemiology
• Mycobacterium Infections, Nontuberculous/immunology
• Nontuberculous Mycobacteria/immunology
• Prognosis
• Retrospective Studies
• Taiwan/epidemiology
• Time Factors

• AIDS-Related Opportunistic Infections/immunology
• AIDS-Related Opportunistic Infections/microbiology
• Adult
• Antifungal Agents/therapeutic use
• Asia, Southeastern/epidemiology
• Child
• Female
• HIV Infections/immunology
• HIV Infections/microbiology
• Humans
• Immunity, Cellular
• Immunocompetence
• Immunocompromised Host
• Immunosuppression Therapy
• Male
• Mycoses/drug therapy
• Mycoses/epidemiology
• Mycoses/immunology
• Mycoses/microbiology
• Penicillium/classification
• Penicillium/isolation & purification
• Talaromyces/isolation & purification

• Autoantibodies/blood
• Case-Control Studies
• Cytokines/biosynthesis
• Humans
• Immunity, Cellular
• Immunologic Deficiency Syndromes/immunology
• Interferon-gamma/immunology
• T-Lymphocytes/immunology

• disseminated non-tuberculous mycobacteria infection
• autoantibody to interferon-γ
• mycobacterium avium

• Aged
• Anti-Bacterial Agents/therapeutic use
• Autoantibodies/blood
• Clarithromycin/therapeutic use
• Ethambutol/therapeutic use
• Humans
• Interferon-gamma/immunology
• Male
• Mycobacterium avium-intracellulare Infection/diagnosis
• Mycobacterium avium-intracellulare Infection/etiology
• Mycobacterium avium-intracellulare Infection/therapy
• Rifampin/therapeutic use

• IFN-γ
• Mendelian susceptibility to mycobacterial diseases (MSMD)
• children
• human genetics
• primary immunodeficiency

• Anti-cytokine
• Autoantibodies
• Autoimmune diseases
• Immunodeficiency
• Opportunistic infections

Cell-mediated immunity plays a crucial role in resistance to intracellular infection. We previously reported antibodies against interferon-gamma (IFN-γ) in HIV− negative (HIV−) patients with acquired immunodeficiency presenting with repeated episodes of disseminated infection caused by uncommon opportunistic intracellular fungal, bacterial, and viral pathogens. This follow-up study aimed to investigate cellular immune responses in these unusual patients.

Twenty HIV− patients presenting with ≥2 episodes of culture- or histopathologic-proven opportunistic infections were enrolled along with age- and sex-matched controls comprised of 20 HIV+ patients plus 20 healthy adults. Monocyte phenotyping and intracellular cytokine production were determined by staining with specific antibodies followed by flow cytometry. Anti-interferon-γ antibodies were measured by enzyme-linked immunosorbent assay, and inducible nitric oxide synthase by reverse-transcription polymerase chain reaction.

There were no differences among cases, HIV+, and healthy controls in the percentage of monocytes, or CD68 and HLA-DR expression on their surfaces. FcR1 (CD119) expression on monocytes was significantly higher in cases than in HIV+ (p<0.05) and healthy controls (p<0.01), suggesting the presence of activated monocytes in the circulation. Interleukin (IL)-2 and tumor necrosis factor (TNF)-α production in CD4 cells were significantly lower in cases than in healthy controls (p<0.01 and p<0.001, respectively). CD8 production of TNF-α among cases was significantly lower than that of healthy controls (p<0.05).

Immunodeficiency in HIV− individuals with repeated infections with intracellular pathogens may be associated with one or more of the abnormal immune responses reflected by the reduced production of both IL-2 by CD4 T cells and TNF-α by CD4 T cells and CD8 T cells, as well as presence of anti-IFN-γ antibody, as previously reported.

• AIDS-Related Opportunistic Infections/immunology
• AIDS-Related Opportunistic Infections/metabolism
• AIDS-Related Opportunistic Infections/virology
• Adolescent
• Adult
• Antibodies/immunology
• Cytokines/biosynthesis
• Female
• HIV Seronegativity/immunology
• Humans
• Immunity, Cellular
• Interferon-gamma/immunology
• Intracellular Space/microbiology
• Male
• Middle Aged
• Monocytes/cytology
• Monocytes/immunology
• Monocytes/metabolism
• Nitric Oxide Synthase Type II/biosynthesis
• Young Adult

• Autoantibody
• Cytokine
• Interferon-γ
• Non-tuberculous mycobacteria
• Pulmonary disease

• Adult
• Aged
• Aged, 80 and over
• Antibodies/blood
• Antibodies/immunology
• Autoantibodies/blood
• Autoantibodies/immunology
• Female
• Granulocyte-Macrophage Colony-Stimulating Factor/immunology
• Humans
• Immunoglobulin G/blood
• Interferon-gamma/immunology
• Lung Diseases/microbiology
• Male
• Middle Aged
• Mycobacterium Infections, Nontuberculous/immunology
• Nontuberculous Mycobacteria/immunology

• Aged
• Anti-Bacterial Agents/therapeutic use
• Autoantibodies/blood
• Female
• Humans
• Interferon-gamma/immunology
• Lymphadenitis/blood
• Lymphadenitis/diagnosis
• Lymphadenitis/etiology
• Mycobacterium Infections, Nontuberculous/blood
• Mycobacterium Infections, Nontuberculous/diagnosis
• Mycobacterium Infections, Nontuberculous/drug therapy
• Mycobacterium fortuitum
• Pneumonia, Bacterial/blood
• Pneumonia, Bacterial/diagnosis
• Pneumonia, Bacterial/etiology