Chediak-Higashi Research Articles

Chediak-Higashi Syndrome: A Case Presenting in Accelerated Phase

Chediak Higashi syndrome (CHS) is an autosomal recessive disorder, caused by biallelic mutations in the highly conserved LYST gene. It is characterized by partial oculocutaneous albinism and immunodeficiency. Approximately 500 cases are reported worldwide. Here we report a case of a twelve years old girl, hospitalized in children’s hospital of Rabat Morocco, who suffered from Chediak higashi syndrome presented in its accelerated phase, the diagnosis was made on the basis of clinical characteristics, hair analysis, and the presence of giant inclusions in peripheral blood smear and in the bone marrow. The only treatment reportedly leading to cure of CHS has been allogeneic hematopoietic stem cell transplantation. Without it, CHS is usually fatal before the age of 10 years because of “accelerated phase” HLH induced by infection. An early diagnosis can improve its prognosis by performing an allogeneic hematopoietic stem cell transplantation before reaching the accelerated phase.

To Study the Role of Bone Marrow Aspiration in Etiological categorization of Pediatric Pancytopenia

Background: Pancytopenia is a Clinico-hematological entity, characterized by a triad of Anemia, leucopenia, and thrombocytopenia. The criterion for defining Pancytopenia is HGB < 9 g/dl: ANC < 1.5 x 109/L and platelet count <100 x 109/L. The main objective of this study is to categorize pediatric pancytopenia’s on etiological basis and to study the age wise incidence.
 Methodology and Results: This is a 5-year study (2016-2021) conducted in tertiary care pediatric referral hospital. All data were expressed as Mean +/ - SD and p value <0.05 is taken as statistically significant. A total of 500 bone marrow smears of pancytopenic patients were studied, of which 60% were boys & 40% girls, 64% constituted Malignant diseases and 36% were benign. Incidence wise, ALL is the most common and pancytopenia being 2nd and together comprises 64% of total cases. Some rare cases like AML –M6 in 2 months old, Chediak higashi syndrome and Familial Hemophagocytic syndrome were noted. Flow cytometry and Molecular genetics were done were ever required.
 Conclusion: Bone Marrow Aspiration is a reliable and sensitive test which can be used in investigation of Pediatric pancytopenia’s and if used meticulously with other routine hematological tests can give a high diagnostic accuracy. ALL is most common in our study (other studies showed Aplastic anemia), AML-M6 in 2 months, LD bodies in bone marrow, HPS were amongst the rare cases

Transplanting a Black Kidney from a Albino – First Case Report

Our case report is the only reported case in literature of transplanting a black coloured kidney successfully from a albino donor. Oculocutaneous albinism is similar to hermansky–pudlak syndrome and chediak higashi syndrome and could lead to more widespread lysosome excretory defects. These defects could lead to accumulation of some intra cellular material, leading to the gross discolouration of the kidney. Hermansky pudlak syndrome is a triad of albinism, platelets lacking dense bodies and storage of ceroid like material in tissues. The manifestations of storage disease are variable and include granulomatous colitis, restrictive lung disease, kidney failure and cardiomyopathy. The autofluorescent material stored in the hermansky pudlak syndrome contains dolichols. Our patient was a living related donor who was having oculocutaneous albinism. Her kidneys were normal functioning but on exposure was black coloured. Post transplant the graft showed ATN and parenchymal dysfunction which later recovered.

Clinical, laboratory and molecular signs of immunodeficiency in patients with partial oculo-cutaneous albinism.

Hypopigmentation disorders that are associated with immunodeficiency feature both partial albinism of hair, skin and eyes together with leukocyte defects. These disorders include Chediak Higashi (CHS), Griscelli (GS), Hermansky-Pudlak (HPS) and MAPBP-interacting protein deficiency syndromes. These are heterogeneous autosomal recessive conditions in which the causal genes encode proteins with specific roles in the biogenesis, function and trafficking of secretory lysosomes. In certain specialized cells, these organelles serve as a storage compartment. Impaired secretion of specific effector proteins from that intracellular compartment affects biological activities. In particular, these intracellular granules are essential constituents of melanocytes, platelets, granulocytes, cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Thus, abnormalities affect pigmentation, primary hemostasis, blood cell counts and lymphocyte cytotoxic activity against microbial pathogens. Among eight genetically distinct types of HPS, only type 2 is characterized by immunodeficiency. Recently, a new subtype, HPS9, was defined in patients presenting with immunodeficiency and oculocutaneous albinism, associated with mutations in the pallidin-encoding gene, PLDN.Hypopigmentation together with recurrent childhood bacterial or viral infections suggests syndromic albinism. T and NK cell cytotoxicity are generally impaired in patients with these disorders. Specific clinical and biochemical phenotypes can allow differential diagnoses among these disorders before molecular testing. Ocular symptoms, including nystagmus, that are usually evident at birth, are common in patients with HPS2 or CHS. Albinism with short stature is unique to MAPBP-interacting protein (MAPBPIP) deficiency, while hemophagocytic lymphohistiocytosis (HLH) mainly suggests a diagnosis of CHS or GS type 2 (GS2). Neurological disease is a long-term complication of CHS, but is uncommon in other syndromic albinism. Chronic neutropenia is a feature of HPS2 and MAPBPIP-deficiency syndrome, whereas it is usually transient in CHS and GS2. In every patient, an accurate diagnosis is required for prompt and appropriate treatment, particularly in patients who develop HLH or in whom bone marrow transplant is required. This review describes the molecular and pathogenetic mechanisms of these diseases, focusing on clinical and biochemical aspects that allow early differential diagnosis.

The pallidin (Pldn) gene and the role of SNARE proteins in melanosome biogenesis.

This review focuses on the product of the pallidin (Pldn) gene, one of a number of genes that in mice are associated with pigmentation defects and platelet dense granule deficiency. A similar combination of defects is also observed in patients suffering from Hermansky-Pudlak (HPS) and Chediak-Higashi (CHS) syndromes. Pldn encodes a novel, approximately 20-kDa protein that is expressed ubiquitously in mammalian tissues. The pallidin protein was found to bind to syntaxin 13, a member of the syntaxin family of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). As SNARE proteins mediate fusion of intracellular membranes, pallidin may play a role in membrane fusion events required for melanosome biogenesis.

Expression of the Chediak-Higashi lysosomal abnormality in human peripheral blood lymphocyte subpopulations

Fusion of lysosomes to form a giant cytoplasmic inclusion is a major abnormality expressed by multiple hematopoietic and non-hematopoietic cell types in Chediak-Higashi (C-H) patients. In this study, the extent of involvement of lymphoid cell subpopulations was defined. Purified populations of B cells, natural killer (NK) cells, and helper T cells were obtained from two C-H patients and normal controls by immunofluorescence staining of their blood mononuclear cells with the monoclonal antibodies HB-2, Leu-7, or Leu-3 followed by fluorescence- activated cell sorting. Cytochemical and ultrastructural analyses as well as functional assays were performed to determine whether or not the C-H lysosomal abnormality was expressed in the different lymphocyte subpopulations. B cells expressed the C-H defect following activation and differentiation. All of the Leu-7+ cells and a significant proportion of the Leu-3+ cells displayed the C-H abnormality. These Leu- 3+ cells share the NK lineage characteristics of granular lymphocyte morphology and the capacity to bind to NK cell targets. In contrast, the C-H abnormality was not observed in non-NK target-binding cells with T helper phenotype, in which clusters of lysosomes formed a normal Gall body. Moreover, T cell functions were unimpaired in C-H patients. These observations raise the issue of the lineal relationship between granular and nongranular lymphocytes typed as T cells on the basis of cell surface antigen markers.

Expression of the Chediak-Higashi Lysosomal Abnormality in Human Peripheral Blood Lymphocyte Subpopulations

Fusion of lysosomes to form a giant cytoplasmic inclusion is a major abnormality expressed by multiple hematopoietic and non-hematopoietic cell types in Chediak-Higashi (C-H) patients. In this study, the extent of involvement of lymphoid cell subpopulations was defined. Purified populations of B cells, natural killer (NK) cells, and helper T cells were obtained from two C-H patients and normal controls by immunofluorescence staining of their blood mononuclear cells with the monoclonal antibodies HB-2, Leu-7, or Leu-3 followed by fluorescence-activated cell sorting. Cytochemical and ultrastructural analyses as well as functional assays were performed to determine whether or not the C-H lysosomal abnormality was expressed in the different lymphocyte subpopulations. B cells expressed the C-H defect following activation and differentiation. All of the Leu-7+ cells and a significant proportion of the Leu-3+ cells displayed the C-H abnormality. These Leu-3+ cells share the NK lineage characteristics of granular lymphocyte morphology and the capacity to bind to NK cell targets. In contrast, the C-H abnormality was not observed in non-NK target-binding cells with T helper phenotype, in which clusters of lysosomes formed a normal Gall body. Moreover, T cell functions were unimpaired in C-H patients. These observations raise the issue of the lineal relationship between granular and nongranular lymphocytes typed as T cells on the basis of cell surface antigen markers.

DEFECTIVE IMMUNOREGULATORY FUNCTION OF LYMPHOCYTES FROM PATIENTS WITH THE CHEDIAK-HIGASHI SYNDROME

Lymphocytes (PBL) from 2 Chediak-Higashi (CH) syndrome patients were examined for natural killer (NK) activity, antibody dependent cellular cytotoxicity (ADCC), target binding capacity (TBC), lectin dependent cellular cytotoxicity (LDCC), Con A induced suppressor cells, soluble suppressor factor (SSF), and responsiveness to interferon (IF) and interleukin-2 (IL-2). PBL from CH patients showed little NK or ADCC activity at various effector to target cell ratios. However, the TBC of patients' PBL was comparable with controls, indicating that the defect in cytotoxicity was not due to lack of target recognition. PBL from CH patients cultured with and without Con A failed to suppress the NK activity of fresh allogeneic effector cells in contrast to normal PBL, suggesting that defects in immunoregulatory lymphocytes may coexist with abnormal effector functions in CH patients. Although residual cytotoxicity of CH lymphocytes could be considerably enhanced with PHA in the LDCC system, enhancement was markedly less than that of normal control cells. Preincubating CH lymphocytes for 24 hr produced a slight increase in NK activity when IF was added to the cultures, whereas IL-2 did not enhance cytotoxicity in contrast when normal PBL were precultured with IF and IL-2. SSF from CH patients significantly inhibited the NK activity of normal PBL. The diminished cytotoxicity, defective immunoregulatory functions and reduced responsiveness to IF, IL-2 and LDCC of PBL from CH patients may contribute to their increased risk of infection and malignancies.

Serotonin accumulation in granules of storage pool-deficient platelets of Chediak-Higashi cattle.

Platelets from cattle with the Chediak-Higashi (CH) syndrome are virtually devoid of dense granules, serotonin (5-HT), and stored ATP and ADP. The present study determined how the handling of 5-HT in normal cattle platelets differed from that in CH cattle platelets. Normal and CH platelets accumulated 5-[14C]HT to the same extent. After normal and CH platelets were incubated with 5-HT for 12 h most 5-HT is still intact, indicating that it was protected from metabolism. Part of the newly acquired 5-HT in normal and CH platelets was in a pool that was rapidly released by 5 U/ml of thrombin, suggesting that 5-HT was, in part, within granules. Subcellular fractionation studies showed that, whereas most of the newly acquired 5-HT in normal platelets was located in the dense granule fractions, about one fourth was found in the lighter granule fraction that was enriched in alpha-granules. The dense granule fraction was virtually absent in CH platelets, and most of the granule 5-HT was associated with the lighter granule fraction. The mixed granule fraction from CH platelets accumulated 5-HT but the uptake was about 10% of that from normal platelets. Unlike normal granules the uptake of 5-HT by CH granules was only slightly inhibited by reserpine but was reversed by NH4Cl and nigericin treatment.

Natural killer (HNK-1+) cells in Chediak-Higashi patients are present in normal numbers but are abnormal in function and morphology.

Children with the Chediak-Higashi (CH) syndrome are known to have abnormalities of natural killer (NK) cell function. We used the HNK-1 monoclonal antibody that reacts specifically with human NK and K cells to distinguish whether this abnormality was due either to a numerical deficiency of NK cells or a defect in their ability to function. In eight CH patients, a significant proportion of their blood mononuclear cells (10--19%) expressed the HNK-1 differentiation antigen. The level of NK cells in the five children with CH syndrome was higher than for age-matched normal controls (15.8% vs. 5.8%, P less than 0.001). When HNK-1+ cells were isolated with a fluorescence-activated cell sorter, the NK cells from CH patients were a homogeneous population of lymphocytes with a single large granule rather than the multiple small granules seen in Nk cells from normal individuals. The purified HNK-1+ cells from the CH patients had minimal NK or K cell function. The CH syndrome thus includes a functionally defective population of NK cells that retain the capability of expressing the HNK-1 differentiation antigen.

Platelet leukocyte interactions. II. In-vivo correction of Chediak-Higashi leukocyte function with serotonin or normal platelets.

The formed elements of the peripheral blood often are characterized according to their separate primary functions in homeostasis. While these elements perform independently of each other, there is increasing evidence documenting an essential interaction between these formed elements. Some of these interactions, for example, have been shown to involve lymphocyte subtypes or lymphocytes and macrophages in cellular and humoral immunity1, and more recently, the relationship of neutrophilic metabolic activation to the platelet release reaction has been demonstrated2–7. We recently have presented evidence for the reversed interaction between neutrophils and platelets where a component of platelet dense bodies affects neutrophil function8. In these studies, platelet-leukocyte interactions were evaluated in-vitro, using the beige mouse, an animal model of the Chediak-Higashi (CH) syndrome, where both platelet and leukocyte function are defective. These studies demonstrated that normal platelets, or serotonin, a constituent of normal platelet-dense bodies which is absent in CH platelets, corrects the abnormal microbicidal activity of CH peripheral blood leukocytes. The present study further tests the hypothesis that platelet serotonin acts as an effector of PMN function be evaluating the effect of intravenous administration of normal platelets or of serotonin on CH leukocyte microbicidal activity, relating our findings to resulting platelet and plasma serotonin levels. The fate of the injected serotonin also was determined, and it was demonstrated that large amounts of the metabolite 5 hydroxyindole acetic acid (5-HIAA) are formed. This substance, however, has no effect on leukocyte function. These studies confirmed our initial in-vitro observations and showed that CH leukocyte function may be corrected in-vivo by normal platelets or serotonin but not by serotonin breakdown products.

Evaluation of the platelet storage pool deficiency in the feline counterpart of the Chediak-Higashi syndrome.

Cats with the Chediak-Higashi (CH) syndrome have abnormal hemostasis with prolonged bleeding times and normal coagulation times. Platelet aggregation induced by serotonin, ADP, and collagen was impaired. Platelets from normal and CH cats were incubated with 14C-adenine and then gel-filtered. Gel-filtered platelets (GFP) from CH cats contained 63% of the ATP, 38% of the ADP, 100% of the Ca2+, and 75% of the Mg25 of normal platelets. Serotonin could not be detected in CH platelets. Acid hydrolase and total platelet protein of CH platelets was similar to normal platelets. Gel-filtered platelets were treated with thrombin to induce maximal secretion. Secretion of ATP, Ca2+, and Mg2+ was 1.9%, 12.4%, and 16% respectively of normal platelets. ADP secretion by CH platelets was not detectable. The ATP/ADP ratio in the 14C-labeled metabolic pool of normal platelets was similar to that of total measured nucleotide pool of CH platelets. These findings suggest that in feline CH platelets, as in platelets from CH mink and cattle, there is storage pool deficiency that is virtually complete, and the virtual absence of ADP and 5HT may in part account for the abnormal hemostasis. Aggregation of platelets from CH cats was impaired, but these platelets did aggregate to arachidonate, serotonin-induced biphasic aggregation, and the aggregation response to ADP and collagen varied according to the amount of serotonin-induced TxB2 formed. These findings support a major role for arachidonate in platelet activation.

Role of NK cells in tumour growth and metastasis in beige mice.

Although natural killer (NK) cells are thought to give the host a spontaneous resistance against tumours and have been postulated to act in vivo as surveillor cells, definitive data in support of these hypotheses has not been obtained. Recently the beige (bg) mouse, a morphological homologue of the human Chediak-Higashi (CH) syndrome, was shown to be deficient in NK activity. Specifically, spleen cells of bg mice were demonstrated to be incapable of in vitro natural cytotoxicity against tumour cells. We report here that a tumour line, modified to be sensitive to NK cytotoxicity by in vitro culture, demonstrated in vivo an increased growth rate, faster induction time and an increased metastatic capability in bg compared to control mice. This was not found with a tumour line insensitive to NK activity (without in vitro culture). In vivo activation of NK cells in bg and control mice resulted in a decrease in tumour growth rate and metastatic frequency. These results demonstrate that NK cells have an important function in the host's control of tumour growth and metastasis.

A dominant role of thromboxane formation in secondary aggregation of platelets.

Aggregation of human platelets in vitro can occur in two phases—primary and secondary aggregation1. Primary aggregation is due to the direct interaction of the aggregating agent with its receptor2,3, whereas secondary aggregation is associated with both the secretion of dense granule constituents, including the aggregating agents, serotonin and ADP (ref. 4) and the activation of a pathway for the conversion of arachidonic acid to prostaglandins (PGs)5. Both secondary aggregation and the associated secretion of dense granule constituents are contingent on the formation of PGG2 and PGH2 which can, in part, be transformed into thromboxane (TX) A2 (refs 1,3,6,7). TXA2 is a potent aggregating agent and apparently the functionally active compound in the arachidonate pathway8–10. However, the precise role of TXA2 in mediating secondary aggregation is a matter of controversy as it is not clear whether secondary aggregation can occur independently of secretion. We report here that platelets from cats with the Chediak–Higashi (CH) syndrome11 aggregate with arachidonate in a cyclooxygenase-dependent manner and that biphasic aggregation produced by serotonin is accompanied by TXB2 formation without detectable ADP secretion. These results demonstrate that secondary platelet aggregation can be mediated through thromboxane formation without participation of secreted ADP.

Characterization of platelets from normal mink and mink with the Chediak-Higashi syndrome.

Bleeding times of mink with the Chediak-Higashi (CH) syndrome was markedly prolonged. Platelet counts were normal but there was an impaired platelet aggregation response to collagen. The metabolic adenine nucleotide pool of platelets from normal and CH mink was labeled with 14C-adenine and the platelets were gel-filtered. Gel-filtered platelets (GFP) from CH mink contained only 37.9% of the adenosine triphosphate (ATP) and 9.6% of the adenosine diphosphate (ADP) found in normal platelets and the ATP/ADP ratio was similar to the 14C-ATP/14C-ADP ratio. Platelet content of Ca2+, Mg2+, and in particular 5-hydroxytryptamine was decreased. When GFP were incubated with thrombin to induce maximal secretion, only negligible amounts of ATP and ADP were released. The specific activity of the extracellular nucleotides approximated that within the platelet. These findings suggest that the stored nucleotide pool in CH platelets is virtually absent and that the abnormalities in platelet function may be due, in part, to the essential absence of secretable ADP and serotonin. The release of Ca2+ and Mg2+ by CH platelets was 56% and 27.8% of normal, respectively.

41 THE EFFECT OF ASCORBATE ON SEVERAL BLOOD CELL FUNCTIONS IN THE CHEDIAK-HIGASHI SYNDROME

The Chedi ak-Higashi (CH) syndrome is an autosomal recessive disorder, associated with oculo-cutaneous albinism, recurrent pyogenic infections, neutropenia, increased bleeding tendency and the occurrence of a “lymphoma-like accelerated” phase. Characteristicly, giant granules are found in all granule-containing cells. We have examined a patient with the CH-syndrome with defects in chemoactic responsiveness and bactericidal activity of the neutrophils (PMN), in the aggregation of the platelets and in the antibody-dependent lymphocytotoxicity. These defects may be explained by abnormal microtubule assembly and/or membrane fluidity. Administration in vivo or in vitro of ascorbate corrected the elevated cyclic AMP levels and the various functions of the neutrophils, partially corrected the arachidonic-acid-induced platelet aggregation, but had no effect on lymphocytotoxicity. Clinically, a dramatic reduction in the number of episodes with recurrent infections was observed during ascorbate treatment.

Role of marrow-derived monocytes and mesangial cells in removal of immune complexes from renal glomeruli.

Phagocytosis of intravenously administered immune complexes by cells in the mesangium was investigated. The model used was that of exchange marrow transplantation between Chediak-Higashi (CH) mice and syngeneic partners after X-irradiation. This model was chosen since marrow-derived macrophages could be differentiated from resident mesangial cells by the presence of the characteristic giant lysosomes in phagocytic cells of the CH mice. Injected immune complexes were cleared normally and localized in the glomerular mesangium in CH or C57BL/6J mice receiving either C57BL/6J or CH marrow. C57BL/6J mice with CH marrow injected with immune complexes prepared with reduced and alkylated antibodies accumulated many cells within the mesangium that contained both giant lysosomes and electron dense deposits. Deposits were not found in cells with subplasmalemmal microfilaments and perpheral dense bodies. Conversely, the cells in the mesangium of CH mice with C57BL/6J marrow that contained electron dense deposits were devoid of giant lysosomes. Based on these observations, we concluded that (a) marrow-derived monocytes contribute to mesangial hypercellularity after deposition of immune complexes and (b) phagocytosis of immune complexes localized in the glomerular mesangium was by marrow-derived monocytes rather than by mesangial cells.

Leukocyte-platelet interactions in a murine model of Chediak-Higashi syndrome

Chediak-Higashi (CH) syndrome, a genetic disease affecting man and other animals, is partially characterized by defective platelets that lack serotonin and dense bodies and by impaired leukocyte function where chemotaxis, degranulation, and bacterial killing are decreased. The effects of normal platelets containing serotonin and of reagent serotonin on the subnormal microbicidal activity of CH leukocytes were evaluated. The peripheral blood leukocytes of the beige mouse, an animal model with CH syndrome, were used with Staphylococcus aureus as the bacterial challenge. Addition of as few as two normal platelets/leukocyte resulted in normal levels of microbicidal activity of CH leukocytes. A similar normalization of leukocyte function was seen when 1-100-micrometer serotonin was added to the incubation mixture. Based on this work and work of others, a plausible explanation for these observations is that normal platelets interact with CH leukocytes, releasing serotonin, which results in reversal of the CH leukocyte defect in bacterial killing.

Leukocyte-Platelet Interactions in a Murine Model of Chediak-Higashi Syndrome

Chediak-Higashi (CH) syndrome, a genetic disease affecting man and other animals, is partially characterized by defective platelets that lack serotonin and dense bodies and by impaired leukocyte function where chemotaxis, degranulation, and bacterial killing are decreased. The effects of normal platelets containing serotonin and of reagent serotonin on the subnormal microbicidal activity of CH leukocytes were evaluated. The peripheral blood leukocytes of the beige mouse, an animal model with CH syndrome, were used with Staphylococcus aureus as the bacterial challenge. Addition of as few as two normal platelets/leukocyte resulted in normal levels of microbicidal activity of CH leukocytes. A similar normalization of leukocyte function was seen when 1-100-micrometer serotonin was added to the incubation mixture. Based on this work and work of others, a plausible explanation for these observations is that normal platelets interact with CH leukocytes, releasing serotonin, which results in reversal of the CH leukocyte defect in bacterial killing.

Prostaglandins and Cyclic Nucleotides in the Chédiak-Higashi Syndrome and Experimental Systemic Lupus Erythematosus

Prostaglandins and cyclic nucleotides are important regulators of cell function and immune/inflammatory responses. Chediak-Higashi (CH) syndrome in man is a genetic disorder characterized by pale skin, hair, and eye color, abnormal lysosomes, and recurrent infections. Oculocutaneous pigment dilution and impaired leukocyte function appear to be due to a defect in microtubule assembly. Whereas human peripheral blood polymor-phonuclear (PMN) leukocytes do not form surface caps with concanavalin A (Con A) except after treatment with agents such as colchicine that inhibit microtubule assembly, CH PMN leukocytes exhibit spontaneous cap formation. This capping is inhibited by cyclic GMP (cGMP) and by cholinergic agonists that increase cellular cGMP generation. The extensive assembly of microtubules seen with the electron microscope in normal human PMN leukocytes incubated with Con A does not occur in PMN leukocytes from CH patients. Incubation of CH PMN leukocytes with cGMP or agents that increase cellular cGMP results in a marked increase in microtubule numbers when cells are exposed to Con A. Because ascorbic acid increases human leukocyte cGMP levels in vitro, CH patients have been treated with vitamin C. Early results in approximately 6 CH patients indicate that vitamin C therapy restores leukocyte function and prevents recurrent infections. A disease similar to human systemic lupus erythematosus develops in New Zealand black and white (NZB/W) mice; it is characterized by impaired cell-mediated immunity, enhanced humoral immune responses, circulating antibodies to nuclear antigens, and immune-complex. glomerulonephritis. Treatment of NZB/w mice with prostaglandin E1 prevents glomerular deposition of immunoglobulins and complement, the development of proliferative glomerulonephritis, and prolongs their survival.