Immunophenotypic pattern of childhood acute lymphoblastic leukemia.

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Primary antibody deficiency in Arabs: first report from eastern Saudi Arabia.

Epidemiological studies have shown wide geographical and racial variations in the prevalence and pattern of immunodeficiency diseases. As there is no national registry, very little is known of the prevalence and nature of humoral immunodeficiency in the Arabian peninsula. We report here for the first time the analysis of serum immunoglobulin (Ig) levels in 2000 consecutive patients (age, 1-80 years). They were seen over a period of 6 years and were referred to us from six district hospitals for suspected immunodeficiency, autoimmunity, allergy, or immunoglobulin dyscrasia. Forty-six were found to be immunodeficient, in whom at least one of the Ig class was low; 15 had secondary immunodeficiency. The remaining 31 cases, representing 1.5% of the population studied (giving a prevalence of 1550/100,000 hospital registered patients), were categorized into four primary humoral immunodeficiency groups: these included, in order of frequency, (i) selective IgA deficiency (45%; 700/100,000) (ii) common variable immunodeficiency (CVID) (29%; 450/100,000), (iii) agammaglobulinemia (16%; 250/100,000), and (iv) selective IgG deficiency (10%; 150/100,000). Compared with similar hospital-based surveys in the west the prevalence of humoral immunodeficiency seems to be higher in Arabs; this in part may be related to race and higher rate of consanguinity. Most patients with IgA deficiency had either infection, atopy or autoimmunity. Compared with some other races, agammaglobulinemia (X- and non-X-linked) seems to be more prevalent.

Common variable immunodeficiency with CD4+ T lymphocytopenia and overproduction of soluble IL-2 receptor associated with Turner's syndrome and dorsal kyphoscoliosis.

An unusual combination of common variable immunodeficiency (CVID) and Turner's syndrome in a Saudi woman aged 20 years is presented. In addition to panhypogammaglobulinaemia, the patient had CD4+ T lymphocytopenia; however, there was evidence of in vivo activation of T cells and overproduction of soluble interleukin 2 receptor in culture supernate. Mantoux test was positive, but lymphoblastic response to non-specific mitogen was impaired. Immunogenetically the patient was HLA-DR3 positive and karyotypically she was a mosaic (45XO/46XX) with ring X chromosome (46Xr(X)). The presence of severe kyphoscoliosis was possibly related to ring X chromosome. This case highlights the grave consequences of the delayed diagnosis of immunodeficiency and emphasises the heterogeneous nature of CVID.

Wessely-type immune ring following phototherapeutic keratectomy.

Immune rings following photorefractive keratectomy (PRK) have been reported but have not been described in detail. This case report describes an immune ring after phototherapeutic keratectomy (PTK) in a patient with long-standing superficial corneal scars. A dense white ring formed in the peripheral cornea on the fourth day following surgery. The patient was treated with antibiotics until negative cultures were reported 48 hours later. A biopsy was taken and examined by light microscopy using hematoxylin-eosin and Mason's trichrome staining. The stroma showed focal keratocyte depopulation with nuclear fragments, occasional polymorphonuclear leucocytes, and an active fibroblastic reaction. No lymphocytes or plasma cells were seen. Clinically, the immune ring faded slowly and was still apparent 9 months after the PTK. Studies of similar cases are required to clarify the mechanisms responsible for this phenomenon.

Ocular toxicity of desferrioxamine: light microscopic histochemical and ultrastructural findings.

This study documents for the first time light and electron microscopical changes in the retinal pigment epithelium (RPE) following treatment with high dose desferrioxamine for systemic iron overload. The changes include loss of microvilli from the apical surface, patchy depigmentation, vacuolation of the cytoplasm, swelling and calcification of mitochondria, and disorganisation of the plasma membrane. In addition, Bruch's membrane overlying degenerate RPE cells appeared abnormally thickened owing to the accumulation of large amounts of mature elastic fibres, pre-elastic oxytalan, and long spacing collagen. The specificity of these changes and the mechanism of toxicity are discussed.

Scrolls of Descemet's membrane as unusual giant nodules on the posterior cornea: histochemical and ultrastructural findings.

Unusual giant nodules on the posterior surface of Descemet's membrane were observed in two out of over 400 corneae examined during routine histopathological reporting. Both of the patients, a 60-year-old man and a 26-year-old woman, had histories of corneal trauma. Neither was associated with chronic keratitis or corneal dystrophy. Light microscopy showed these nodules to be composed of material resembling Descemet's membrane. Histochemical and electron microscopical preparations identified oxytalan fibres within the outer layers of the nodules. These fibres are not a feature of the normal adult Descemet's membrane. The findings are discussed and compared with other nodular lesions of Descemet's membrane.

Contraction of scar tissue in the rabbit vitreous.

Sheets of vitreous membrane (scar tissue) and associated retinal detachment were produced in the right eye of 86 adult New Zealand white rabbits by intravitreal injection of cultured autologous skin fibroblasts. The membranes were examined by light and electron microscopy and time-lapse cinephotomicrography. Immunohistochemistry was used to demonstrate alterations in the distribution of cytoplasmic contractile proteins. While retinal detachment and membrane contraction were taking place, there was pronounced increase in the numbers of fibroblasts with an elongated spindle shape. These spindle-shaped cells had some similarities to myofibroblasts including the presence of 'stress cables'. However, the myofibroblast-like cells stained much less avidly for cytoplasmic (actin) microfilaments than migratory fibroblasts seen at early stages of membrane development. The significance of migrating fibroblasts and myofibroblasts in scar contraction is discussed.

Physiological and pathobiological significance of ocular glycoproteins. I. Studies using fluorescein labelled glycine max.

Cell surface carbohydrates play an important role in several biological, immunological, and neoplastic phenomena including development, growth regulation, cellular locomotion, receptor activation, and tumour metastasis. Fluorescein labelled lectins which bind to specific carbohydrate residues in glycoproteins and glycolipids are being increasingly used as chemical probes to study cell components. Several different preparations of ocular tissues from human, rabbit, and rat were examined for the distribution of N-acetyl-D-galactosamine (D-gal NAc) by means of fluorescein-labelled lectin from soybean (glycine max). A very strong fluorescence was observed in the corneal epithelium; Descemet's membrane and corneal endothelium were also strongly fluorescent. The conjunctival epithelium similarly showed a strong reaction, as did the goblet cells. The iris epithelium and the dilator pupillae were only weakly fluorescent, but the ciliary body showed strong fluorescence, as did the blood vessels. As compared with lens fibres the lens epithelium was strongly fluorescent. The outer retina, that is, the photoreceptors, the pigment epithelium, and Bruch's membrane, showed a very strong reactivity. The optic nerve showed moderate fluorescence, but reaction with extraocular muscles was variable. The skin of the upper and lower eyelids, hair follicles, and blood vessels showed strong lectin binding. Sections of retinoblastoma and malignant melanoma showed no reaction. The physiological and pathological significance of these findings is discussed.

New concepts in the control of ocular inflammation.

Recent advances in the field of cellular immunology have enabled us to recognise a complex homeostatic mechanism controlling inflammation, allowing us to understand the aetiopathogenesis of many systemic disease processes. This immune regulatory mechanism involves the interaction of positive and negative messages passing between the different subsets of peripheral blood lymphocytes. Quantitative or qualitative defects in the suppressor cell subset of thymus derived T-lymphocytes are believed to be responsible (at least in part) for chronic inflammation and autoimmune disease. A variety of peripheral blood lymphocyte parameters were examined in four ill-understood inflammatory ophthalmological conditions: acute anterior uveitis, heterochromic cyclitis, acute lepromatous uveitis and Mooren's ulcer. Defects in the number or function of suppressor T-cells were found in all conditions studied. These findings make it possible to explain some of the immunological aberrations previously reported in these conditions. As abnormalities have been found in the immune regulatory mechanism of patients with inflammatory eye conditions of unknown aetiology, the way is now open to explore new lines of treatment using drugs which have the properties to allow selective manipulation of T-lymphocyte subsets.

Retinal and epiretinal glia--an immunohistochemical study.

Immunohistochemical techniques were used to examine the distribution of cells containing glial fibrillary acidic protein (GFAP) in normal and pathological human specimens, including 22 globes (13 of which contained epiretinal membranes 'in situ'), 16 surgically excised epiretinal membranes, and monolayers of cells obtained from five epiretinal membranes placed in tissue culture. The astrocytic cells of normal and pathological retinae stained with the glial-cell marker, but Müller cells were GFAP-negative in normal retinae at the antisera dilutions used. Müller cells did, however, stain in retinae from glaucomatous eyes and in eyes with prolonged retinal detachment. Electron microscopy did not reveal any obvious morphological difference between the intermediate filaments of normal (GFAP-negative) and GFAP-positive Müller cells. Ten of the 13 epiretinal membranes 'in situ', all 16 excised membranes, and three of the five monolayers contained glial cells. Purely glial membranes were not associated with retinal puckering or detachment, while all membranes causing tractional complications had a prominent fibrous, non-glial component. Our findings suggest that glial cells do not contribute significantly to the contractile forces generated by epiretinal membranes. They may, however, provide a scaffold on which other cells proliferate and contract and an anchorage by means of which tangential forces are transmitted into and through the retina.

T-lymphocyte subpopulations in uveitis.

Following an inconclusive study of differential lymphocyte counts in uveitis in which the peripheral blood was examined only once in the course of each case a longitudinal study has been carried out in patients with acute anterior uveitis. Venous blood lymphocytes were examined at intervals throughout the course of the illness, from presentation until six months later. No changes in E-rosetting T cells or total lymphocyte values have been found, nor any variations from normal in the helper (OKT4)/suppressor (OKT8) T-cell ratio. Random studies performed in a sample of patients with heterochromic cyclitis have also failed to reveal consistent abnormalities in peripheral blood lymphocyte parameters.

Acute anterior uveitis and hepatitis B virus infection.

The aetiology of acute anterior uveitis (AAU) in the great majority of cases is unclear. Various infective agents have been postulated, however, as playing a direct or indirect part in the disease process, possibly via an immune-complex vasculitis. In an earlier study we concluded that, contrary to a previous report, hepatitis B virus (HBV) played only a small role, if any, in the pathogenesis of uveitis in Great Britain. Since we did not look for other markers of HBV infection other than hepatitis B surface antigen (HBsAg), it is possible that some cases of recent HBV infection may have been missed. In the present study 49 patients with AAU were tested for markers of hepatitis B infection. Sera from all patients tested were found to be negative for HBsAg and for antibody to the HBV core (anti-HBc), excluding HBV as a significant cause of AAU in this country. Since the quest for an infective agent in AAU may remain unproductive, future research on the aetiopathogenesis of AAU should include the study of tissue 'vulnerability' and the local and systemic immunoregulatory factors which modulate inflammatory responses.

Pathogenesis of Mooren's ulcer: some new concepts.

Mooren's ulcer is a chronic, painful corneal ulceration of unknown aetiology. Recent histological and immunological studies suggest an autoimmune basis. It is now becoming clear that the immune system plays an intricate role in maintaining homoeostasis in health and disease. Regulation of the immune response appears to involve a subset of peripheral blood T lymphocytes known as suppressor cells. A qualitative or quantitative deficiency of suppressor cells may therefore be responsible for chronic inflammation, autoimmune disease, and immunodeficiency states. To explain the reported immunological aberrations the number of suppressor T cells in addition to other immunological parameters were studied in a patient with bilateral Mooren's ulcers. A deficiency of suppressor T cells was found in the peripheral blood. This deficit in the immunoregulatory mechanism explains some of the immunological abnormalities reported in previous studies. Furthermore this study provides additional evidence for an autoimmune aetiology. In the light of these findings the possibility of a new line of treatment has been raised.