Laboratory Studies
Since the prognosis depends on a presymptomatic diagnosis and early treatment before complications occur, a simplified, practical and economic newborn screening method would be highly desirable and has been suggested. [19, 20]
In patients with Omenn syndrome, the peripheral WBC count may be normal or elevated with a predominance of lymphocytes. Eosinophilia is invariably present.
Flow cytometry should include the customary T, B, and natural killer cell (NKC) markers with additional T-cell markers including CD25, CD30, human leukocyte antigen (HLA)–DR, CD95, and CD69. CD25 is expressed in Treg cells as well as in the effector T cells while CD30 is expressed in activated T and B cells. CD45RO and CD45RA are used to identify cells responding to antigen stimulation and naïve T cells.
See the Differential Diagnosis section of the Medscape Reference article Pediatric Severe Combined Immunodeficiency for a table of the lymphocyte profiles characteristic for various T-cell disorders.
The results show the presence of an oligoclonal set of activated antigen-stimulated Th2 cells.
B cells are absent, and NKC are present. T cells may have normal distribution of CD4 and CD8 or a predominance of CD8.
Immunoglobulin levels show absent immunoglobulin A (IgA) and immunoglobulin M (IgM), elevated IgE levels, and immunoglobulin G (IgG) that is maternal in origin. IgG antibodies against T-dependent antigens, such as tetanus, are nonprotective. Specific IgM antibodies, such as isohemagglutinins, are absent.
Lymphocyte mitogen responses to phytohemagglutinin (PHA), concanavalin A (conA), and pokeweed mitogen (PWM) are absent or profoundly decreased. In contrast, response to anti-CD3, superantigens, and phorbol myristate acetate (PMA)/ionomycin may be detectable. Addition of interleukin 2 (IL-2) can enhance the latter responses.
Cultures and the histologic examination of tissues and body fluids for infectious agents are mandatory for appropriate management of the infections.
When a T-cell disorder is suspected, the Immune Deficiency Foundation has a consultative service for physicians. Laboratories in New York City and at the University of Washington in Seattle and at the Children's Hospital in Boston are funded by the Jeffrey Modell Foundation. They provide molecular analysis or assistance in contacting other research facilities.
Imaging Studies
The thymus is absent on chest radiographs of most forms of severe combined immunodeficiency (SCID), including Omenn syndrome.
In the initial workup or if fever develops, look for pulmonary infiltrates due to viral infections and interstitial pneumonitis caused by P carinii.
Other Tests
Perform mutational analysis for RAG-1 and RAG-2 to permit genetic counseling and prenatal diagnosis in subsequent pregnancies. Other mutation analysis may be indicated depending on clinical features.
Serum interleukin 4 (IL-4) and interleukin 5 (IL-5) levels are typically increased. In vitro cells produce decreased levels of IL-2 and interferon-gamma (IFN-γ) compared with the elevated IL-4 and IL-5 production by Th2 cells. These findings are consistent with decreased T helper 1 (Th1) cell activity.
Molecular analysis of HLA alleles by means of the polymerase chain reaction (PCR) or restriction fragment length polymorphism (RFLP) may be needed to detect engraftment of maternal T cells or graft versus host disease (GVHD) from transfusion-associated cells.
Procedures
Skin biopsy may be considered, although an experienced immunologist may be able to make the diagnosis without this data in the appropriate clinical setting. The presence of maternally engrafted cells is more sensitively assessed with DNA techniques and peripheral blood lymphocytes, as indicated above.
Lymph node biopsy is unlikely to contribute additional information; fluorocytometric analysis of peripheral blood lymphocytes and lymphocyte mitogen assays provide more detailed diagnostic data.
Bronchoscopy is frequently necessary to identify P carinii, viral, and fungal etiologies of pulmonary infection.
Histologic Findings
Skin biopsy findings reveal psoriasiform hyperplasia of the epidermis with parakeratosis, cellular dyskeratosis, and necrosis. The skin may show an infiltration of CD4+ (helper) T cells typically, but has been described with CD8+ (cytotoxic) T cells instead. [21]
The partial T-cell defects result in infiltration of the skin, with activated autoreactive T cells expressing CD30 and CD45RO. Eosinophils and histiocytes also populate the skin.
Reactive lymph nodes show infiltrating eosinophils and histiocytic cells but lack germinal centers and cortical T lymphocytes.
The gut lacks lymphocytes in Peyer patches and in the lamina propria.
Rudimentary thymic tissue shows poorly formed and decreased Hassall corpuscles with few lymphocytes.
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A unique dermatitis characterizes Omenn syndrome. The dermatitis initially resembles eczema, but with a pachydermia, as observed here. The lesions progress to desquamation. Failure to thrive is evident. This infant weighed 6 pounds at age 6 months; his weight had not changed since birth.
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Common viral infections are fatal in severe combined immunodeficiency (SCID). This female infant died before bone marrow stem cell engraftment could occur, when varicella became resistant to acyclovir. The nasal bridge reveals superinfection with Klebsiella pneumoniae. Lymphedema, a characteristic of Omenn syndrome, is also shown.
Tables
Brand(Manufacturer) |
Manufacturing Process |
pH |
Additives (IVIG products containing sucrose are more often associated with renal dysfunction, acute renal failure, and osmotic nephrosis, particularly with preexisting risk factors [eg, history of renal insufficiency, diabetes mellitus, age >65 y, dehydration, sepsis, paraproteinemia, nephrotoxic drugs].) |
Parenteral Form and Final Concentrations |
IgA Content (mcg/mL) |
Carimune NF (CSL Behring) |
Kistler-Nitschmann fractionation; pH 4 incubation, nanofiltration |
6.4-6.8 |
6% solution: 10% sucrose, < 20 mg NaCl/g protein |
Lyophilized powder 3%, 6%, 9%, 12% |
Trace |
Flebogamma (Grifols USA) |
Cohn-Oncley fractionation, PEG precipitation, ion-exchange chromatography, pasteurization |
5.1-6 |
Sucrose free, contains 5% D-sorbitol |
Liquid 5% |
< 50 |
Gammagard Liquid 10% (Baxter Bioscience) |
Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation |
4.6-5.1 |
0.25M glycine |
Ready-for-use Liquid 10% |
37 |
Gamunex (Talecris Biotherapeutics) |
Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation |
4-4.5 |
Contains no sugar, contains glycine |
Liquid 10% |
46 |
Gammaplex (Bio Products) |
Solvent/detergent treatment targeted to enveloped viruses; virus filtration using Pall Ultipor to remove small viruses including nonenveloped viruses; low pH incubation |
4.8-5.1 |
Contains sorbitol (40 mg/mL); do not administer if fructose intolerant |
Ready-for-use solution 5% |
< 10 |
Iveegam EN (Baxter Bioscience) |
Cohn-Oncley fraction II/III; ultrafiltration; pasteurization |
6.4-7.2 |
5% solution: 5% glucose, 0.3% NaCl |
Lyophilized powder 5% |
< 10 |
Polygam S/D Gammagard S/D (Baxter Bioscience for the American Red Cross) |
Cohn-Oncley cold ethanol fractionation, followed by ultracentrafiltration and ion exchange chromatography; solvent detergent treated |
6.4-7.2 |
5% solution: 0.3% albumin, 2.25% glycine, 2% glucose |
Lyophilized powder 5%, 10% |
< 1.6 (5% solution) |
Octagam (Octapharma USA) 9/24/10: Withdrawn from market because of unexplained reports of thromboembolic events |
Cohn-Oncley fraction II/III; ultrafiltration; low pH incubation; S/D treatment pasteurization |
5.1-6 |
10% maltose |
Liquid 5% |
200 |
Panglobulin (Swiss Red Cross for the American Red Cross) |
Kistler-Nitschmann fractionation; pH 4, trace pepsin, nanofiltration |
6.6 |
Per gram of IgG: 1.67 g sucrose, < 20 mg NaCl |
Lyophilized powder 3%, 6%, 9%, 12% |
720 |
Privigen Liquid 10% (CSL Behring) |
Cold ethanol fractionation, octanoic acid fractionation, and anion exchange chromatography; pH 4 incubation and depth filtration |
4.6-5 |
L-proline (approximately 250 mmol/L) as stabilizer; trace sodium; does not contain carbohydrate stabilizers (eg, sucrose, maltose) |
Ready-for use liquid 10% |
< 25 |
