Normal Numbers Of Lymphocytes Research Articles

Atypical Presentations of Hypomorphic X-Linked SCID

RationaleIL2RG mutations are associated with X-linked Severe Combined Immunodeficiency (X SCID). There is increasing awareness of Hypomorphic SCID associated with IL2RG variants; we present 3 novel mutations of this gene with variable presentations. MethodsChart review was performed for patients with hypomorphic SCID due to pathogenic IL2RG variants. Plasmablast differentiation was performed from peripheral blood mononuclear cells using CD40L and IL-21 stimulation for 6 days followed by staining for plasmablast markers (CD19+/CD27+/CD38+) and surface immunoglobulins. ResultsPatient 1 is a 7-year-old Honduran boy with history of recurrent sinopulmonary infections including recent CMV pneumonitis, bronchiectasis, chronic lung disease, food allergies, unilateral retinal detachment, and hydrocephalus s/p VP shunt. Immunologic testing showed elevated lymphocyte numbers with decreased memory B cells, normal immunoglobulins, absent vaccine responses, and poor proliferation to mitogens. Whole genome testing showed two mosaic mutations in IL2RG: c. 568C>T (20%), c. 589T>C (87%). He is on prophylaxis with azithromycin and trimethoprim/sulfamethoxazole, immunoglobulin, and awaiting definitive treatment. Patient 2 is a 10-year-old with recurrent sinopulmonary disease with bronchiectasis. He had normal TRECs, normal lymphocyte numbers with normal mitogen proliferation to PHA, normal immunoglobulin levels, but absent vaccine responses, and abnormal plasmablast differentiation (0.12% CD27+/CD38+ at day 6 post in vitro activation) and profoundly decreased expression of surface IgG and IgA in vitro. Genetic testing showed a hemizygous IL2RG c.32T>C mutation, as well as CFTR mutations (c.1972dup and c.1977_1985del, in cis). He is maintained on immunoglobulin replacement. Patient 3 is a 40-year-old who had recurrent infections beginning in childhood, and extranodal B-cell lymphoma at age 26 years. He had pan-lymphopenia, and genetic testing showed IL2RG c.982C>T, p.R328X. He underwent successful bone marrow transplantation from a matched sibling at age 36. ConclusionsHypomorphic X-SCID due to novel or mosaic variants in IL2RG can present with variable symptoms including malignancy and variable lymphocyte phenotype including normal T, B, and NK cell counts, and should be considered in males with opportunistic or persistent infections. [Display omitted]

Laboratory indicators in patients with non-severe new coronavirus infection COVID-19

The article presents literature data on changes in labo-ratory parameters in new coronavirus infection COVID-19 and the results of our own researches. It was found that in the first three days after hospitalization, most patients had normocytosis, a normal number of lymphocytes. In the mild form, there were slightly more people with normal or with an increased number of leukocytes, granulocytes, but in moderate course, leukopenia, lymphopenia, granulocytosis and granulocytopenia, thrombocytosis, thrombocytopenia were registered more often. At the same time, in the mild form, there were more patients with an increased number of band neutrophils. In mild course, there were no individuals with an increased number of band neutrophils after 3 days in the hospital. Leukocytosis, lymphopenia, granulocytosis were no longer detected after 6 days in the hospital; during this period, the number of patients with leukopenia, thrombocytopenia also decreased significantly, most people had normocytosis. In patients with moderate-to-severe course, leukocytosis and leukopenia were observed for a longer period than with the mild course, even after 10 days in hospital. Most patients had normocytosis. By the sixth day of hospital stay, there were more individuals with granulocytosis (no such patients were registered at a later date), with an increased number of band neutrophils. After 6 days, there was greater number of patients with lymphocytosis, thrombocytosis and lymphocytopenia.

Long-term persistent mixed chimerism in a patient with Wiskott–Aldrich syndrome after allogeneic hematopoietic stem cell transplantation

The article describes a clinical case of a patient with Wiskott–Aldrich syndrome, in whom long- term persistence of mixed chimerism was determined after hematopoietic stem cell transplantation (HSCT) from a haploidentical donor. Based on the analysis of the patient's clinical picture after HSCT, it was shown that the presence of> 50% of donor cells in the myeloid lineage is necessary for the correction of thrombocytopenia. In addition, the presence of mixed chimerism in B-lymphocytes possibly contributed to the development of autoimmune complications in the patient, as well as to the persistent hypogammaglobulinemia, despite the restoration of the normal numbers of lymphocytes in all main sub-populations. The role of mixed chimerism in the pathogenesis of immune post-transplant complications requires study in large groups of patients with primary immunodeficiencies. The patient's parents agreed to use the information, including the child's photo, in scientific research and publications.

Soluble FAS ligand is not required for pancreatic islet inflammation or beta-cell destruction in non-obese diabetic mice

CD8+ T cells play a central role in beta-cell destruction in type 1 diabetes. CD8+ T cells use two main effector pathways to kill target cells, perforin plus granzymes and FAS ligand (FASL). We and others have established that in non-obese diabetic (NOD) mice, perforin is the dominant effector molecule by which autoreactive CD8+ T cells kill beta cells. However, blocking FASL pharmacologically was shown to protect NOD mice from diabetes, indicating that FASL may have some role. FASL can engage with its receptor FAS on target cells either as membrane bound or soluble FASL. It has been shown that membrane-bound FASL is required to stimulate FAS-induced apoptosis in target cells, whereas excessive soluble FASL can induce NF-κB-dependent gene expression and inflammation. Because islet inflammation is a feature of autoimmune diabetes, we tested whether soluble FASL could be important in disease pathogenesis independent of its cell death function. We generated NOD mice deficient in soluble FASL, while maintaining expression of membrane-bound FASL due to a mutation in the FASL sequence required for cleavage by metalloproteinase. NOD mice lacking soluble FASL had normal numbers of lymphocytes in their spleen and thymus. Soluble FASL deficient NOD mice had similar islet inflammation as wild-type NOD mice and were not protected from diabetes. Our data indicate that soluble FASL is not required in development of autoimmune diabetes.

CD275-Independent IL-17-Producing T Follicular Helper-like Cells in Lymphopenic Autoimmune-Prone Mice.

T cells undergo homeostatic expansion and acquire an activated phenotype in lymphopenic microenvironments. Restoration of normal lymphocyte numbers typically re-establishes normal homeostasis, and proinflammatory cytokine production returns to baseline. Mice deficient in guanine nucleotide exchange factor RasGRP1 exhibit dysregulated homeostatic expansion, which manifests as lymphoproliferative disease with autoantibody production. Our previous work revealed that autoreactive B cells lacking RasGRP1 break tolerance early during development, as well as during germinal center responses, suggesting that T cell-independent and T cell-dependent mechanisms are responsible. Examination of whether a particular T cell subset is involved in the breach of B cell tolerance revealed increased Th17 cells in Rasgrp1-deficient mice relative to control mice. Rasgrp1-deficient mice lacking IL-17R had fewer germinal centers, and germinal centers that formed contained fewer autoreactive B cells, suggesting that IL-17 signaling is required for a break in B cell tolerance in germinal centers. Interestingly, a fraction of Th17 cells from Rasgrp1-deficient mice were CXCR5(+) and upregulated levels of CD278 coordinate with their appearance in germinal centers, all attributes of T follicular helper cells (Tfh17). To determine whether CD278-CD275 interactions were required for the development of Tfh17 cells and for autoantibody, Rasgrp1-deficient mice were crossed with CD275-deficient mice. Surprisingly, mice deficient in RasGRP1 and CD275 formed Tfh17 cells and germinal centers and produced similar titers of autoantibodies as mice deficient in only RasGRP1. Therefore, these studies suggest that requirements for Tfh cell development change in lymphopenia-associated autoimmune settings.

BMS-936564 (Anti-CXCR4 Antibody) Induces Specific Leukemia Cell Mobilization and Objective Clinical Responses In CLL Patients Treated Under a Phase I Clinical Trial

Expression of CXCR4 receptor (CD184) has been reported in different malignancies including Chronic Lymphocytic Leukemia (CLL) and the CXCR4-CXCL12 axis has been described to play a very important role in cancer development. Moreover, this pathway can be inhibited using CXCR4 antagonists.Previously, we have shown that BMS-936564, an anti-CXCR4 IgG4 antibody, can block in vitro the CXCR4/CXCL12 pathway in CLL overcoming stromal cell protection by inducing apoptosis, inhibiting F-actin polymerization, and migration of cells. These findings provide the rationale for an ongoing phase I clinical study in which CLL subjects received four weekly infusions of BMS-936564 antibody followed by 5 monthly cycles of bendamustine, rituximab and BMS-936564 antibody (BRB chemoimmunotherapy). Eleven (n=11) subjects with relapse / refractory disease have been enrolled and treated in this study. Here, we present correlative studies performed in three of those CLL subjects with samples collected at different time points (day 1, 2, 8, 15 and 22) during the monotherapy cycle of BMS-936564.All three subjects showed leukocytosis that was detected as early as in 4 hours following the initial BMS-936564 infusion (median increase of 64.6% above base line; range: 59.7% - 112.7%). Leukocytosis was present during the entire four weeks of monotherapy with BMS-936564. Leukocytosis in these three patients was due primarily to increase in absolute counts of CLL cells (Median increase of 129.6%; range: 95.3% - 324.8%). Interestingly, there was no evidence of increase in the absolute number of normal lymphocytes. Only one of the three patients showed an increase in neutrophil counts after infusion of BMS-936564.We observed changes in the level of CXCR4 expression after infusion with BMS-936564. All subjects showed CXCR4 down-regulation in peripheral CLL cells with a median percentage decrease in the level of expression of 106.7% (Range: 25.1% - 350.7%). We did not observe changes in CXCR4 expression in normal B cells.In contrast to our in vitro studies where we observed that all tested CLL samples underwent apoptosis after treatment with BMS-936564, only one subject showed significant increase in the percentage of apoptosis after infusion of BMS-936564 in vivo. The levels of apoptosis detected were relatively low (<18%) and this suggests a potential mechanism of rapid clearance of apoptotic cells.Importantly, associated with the mobilization of CLL cells, all three patients showed significant decrease in the lymphadenopathy size with a median decrease of 59.83% (Range: 55.6-72%). Lymphadenopathy response was assessed using stringent IWCLL response assessment criteria by an independent radiologist using CT scan measurements.All three subjects tolerated the infusions well with no evidence of side effects or toxicities. After the initial monotherapy treatment phase with BMS-936564 antibody, all three subjects received BRB chemoimmunotherapy combination and had a dramatic decrease in lymphocytosis during the first week after initiation of combination therapy. These subjects are currently finishing treatment under protocol and response assessments will be presented during the meeting.In conclusion, we found that BMS-936564 infusion in subjects with CLL induces specific leukemia cell mobilization associated with an objective decrease in the lymphadenopathy bulk and phenotypic changes associated with CXCR4 down-regulation in peripheral leukemia cells. These findings strongly suggest a CXCR4-CXCL12 dependent mobilization process of CLL cells from lymphatic tissues. Together, our study provides for the first time evidence at in vivo level, which supports inhibition of the CXCR4-CXCL12 pathway mediated by BMS-936564 in CLL patients. These findings suggest a compartmental biological distribution and recirculation of CLL cells opening the possibility to explore targeted therapies against minimal residual disease that traditionally has been refractory to conventional chemoimmunotherapy treatment and contributes to the incurable characteristics of this disease. Disclosures:Kuhne:Bristol-Myers Squibb: Employment. Cohen:Bristol-Myers Squibb: Employment. Sabbatini:Bristol-Myers Squibb: Employment. Kipps:Bristol-Myers Squibb: Research Funding. Cardarelli:Bristol-Myers Squibb: Employment.

Neonatal bone marrow transplantation of ADA-deficient SCID mice results in immunologic reconstitution despite low levels of engraftment and an absence of selective donor T lymphoid expansion

AbstractAdenosine deaminase (ADA)–deficient severe combined immune deficiency (SCID) may be treated by allogeneic hematopoietic stem cell transplantation without prior cytoreductive conditioning, although the mechanism of immune reconstitution is unclear. We studied this process in a murine gene knockout model of ADA-deficient SCID. Newborn ADA-deficient pups received transplants of intravenous infusion of normal congenic bone marrow, without prior cytoreductive conditioning, which resulted in long-term survival, multisystem correction, and nearly normal lymphocyte numbers and mitogenic proliferative responses. Only 1% to 3% of lymphocytes and myeloid cells were of donor origin without a selective expansion of donor-derived lymphocytes; immune reconstitution was by endogenous, host-derived ADA-deficient lymphocytes. Preconditioning of neonates with 100 to 400 cGy of total body irradiation before normal donor marrow transplant increased the levels of engrafted donor cells in a radiation dose–dependent manner, but the chimerism levels were similar for lymphoid and myeloid cells. The absence of selective reconstitution by donor T lymphocytes in the ADA-deficient mice indicates that restoration of immune function occurred by rescue of endogenous ADA-deficient lymphocytes through cross-correction from the engrafted ADA-replete donor cells. Thus, ADA-deficient SCID is unique in its responses to nonmyeloablative bone marrow transplantation, which has implications for clinical bone marrow transplantation or gene therapy.

A role for thymic stromal lymphopoietin in CD4(+) T cell development.

Thymic stromal lymphopoietin (TSLP) signals via a receptor comprising the interleukin (IL)-7 receptor α chain and a distinctive subunit, TSLP receptor (TSLPR), which is most related to the common cytokine receptor γ chain, γc. We have generated TSLPR knockout (KO) mice and found that although these mice had normal lymphocyte numbers, γc/TSLPR double KO mice had a greater lymphoid defect than γc KO mice. This indicates that TSLP contributes to lymphoid development and accounts for some of the residual lymphoid development in γc KO mice and presumably in patients with X-linked severe combined immunodeficiency. Injection of TSLP into γc KO mice induced the expansion of T and B cells. Moreover, sublethally irradiated TSLPR KO mice showed weaker recovery of lymphocyte populations than wild-type (WT) littermates, even when neutralizing anti–IL-7 antibodies were injected. Interestingly, TSLP preferentially stimulated the proliferation and survival of CD4+ single positive thymocytes and peripheral T cells in vitro. Additionally, CD4+ T cells from TSLPR KO mice expanded less efficiently than WT CD4+ T cells in irradiated hosts, and TSLP preferentially expanded CD4+ T cells both in vitro and in vivo. Thus, as compared with other known cytokines, TSLP is distinctive in exhibiting a lineage preference for the expansion and survival of CD4+ T cells.

Polysaccharide antibody responses are impaired post bone marrow transplantation for severe combined immunodeficiency, but not other primary immunodeficiencies.

Established treatment of severe combined immunodeficiencies (SCID) and other primary immunodeficiencies (PID) is bone marrow transplantation (BMT). Normal lymphocyte numbers and protein antigen responses are present within 2 years of BMT, polysaccharide antibody responses appear last. Streptococcus pneumoniae infection causes significant morbidity and mortality post-BMT. Previous studies have shown good protein antigen responses post-BMT for SCID and PID, but had not examined the polysaccharide responses. We retrospectively analysed pneumococcal polysaccharide (PPS) responses in our patient series. In total, 22 SCID and 12 non-SCID PID were evaluated, all >2 years post BMT: 17 SCID, 12 PID received chemotherapy conditioning; 17 SCID, three PID had T-cell depleted (TCD) BMT, others had nonconditioned whole marrow BMT. All had normal Haemophilus influenza B and tetanus antibody responses. Of 22 SCID, 13 vs 11/12 PID responded to PPS vaccine (P=0.05). There was no association with donor age, GvHD, B-cell chimerism, or IgG2 level. Fewer TCD marrow recipients responded to PPS (P=0.04). Analysis of the SCID group showed no association of PPS response with type of marrow received. This is the first study to specifically examine PPS antibody responses following SCID and PID BMT. Pneumococcal conjugate vaccine antibody responses should be examined in these children.

Pestivirus in cattle: experimentally induced persistent infection in calves.

Twenty-two heifers were infected intranasally with non-cytopathic bovine viral diarrhoea virus (BVDV) between days 74 and 82 of pregnancy. All animals had developed serum antibodies against BVDV 5 weeks later. No clinical effects were seen in the heifers, and they all delivered a live calf. The newborn calves were generally small, appeared unthrifty as typical 'poor doers', and some developed secondary infections with diarrhoea and signs of respiratory disease. Eighteen of the 22 calves were born without antibodies against BVDV and were persistently infected (PI) with the virus. One was weak at birth and died the following day. Four calves were born with serum antibodies against BVDV and with no detectable virus. Three of these showed signs and/or pathological changes indicating disease in the central nervous system. Otherwise, there were no obvious clinical differences between these calves and the PI calves, nor were there any apparent significant differences in blood parameters between these groups. In general, the calves showed low gamma-globulin values and thrombocytopaenia, but moderately increased fibrinogen values and relatively normal lymphocyte numbers.

Diagnosis of immunodeficiency: clinical clues and diagnostic tests.

Recognition of immunodeficiency allows steps to be taken to minimize morbidity and mortality. Immunodeficiency can be secondary to viral infection, most importantly secondary to HIV-1 worldwide, medications, disruption of the usual infection clearance mechanisms, or secondary to a myriad of systemic disorders. Immunodeficiency may also be due to one of the growing list of primary immunodeficiency disorders. In infancy, lymphopenia should trigger an evaluation investigating the possibility of severe combined immunodeficiency. Evaluations of children should be done keeping in mind that normal numbers of lymphocytes are higher in children than in adults, immunoglobulin levels in children are lower than in adults in younger age groups, and antibody production in response to polysaccharide antigens is not usually fully developed in the less-than 2-year-old child.

Homozygous deletion of the CYP21A-TNXA-RP2-C4B gene region conferring C4B deficiency associated with recurrent respiratory infections

The central class III region of the human major histocompatibility complex contains highly polymorphic genes that are associated with immune disorders and may serve as susceptibility factors for viral infections. Many HLA haplotype specific rearrangements, duplications, conversions and deletions, occur frequently in the C4 gene region. Genetic deficiencies of complement components are associated with recurrent occurrence of bacterial infections. We have studied the complement profile and the class III genes 5′-RP1-C4A-CYP21A-TNXA-RP2-C4B-CYP21B-TNXB-3′ in a 4-year-old Caucasian patient. He has suffered from several pneumonias caused by respiratory viruses, eight acute otitis media, prolonged respiratory infections and urinary tract infection. Complement C4 was constantly low, but the other complement components, from C1 to C9, C1INH, factor B and properdin, were within normal limits. Immunological evaluation gave normal lymphocyte numbers and functions with the exception of subnormal T cell response to pokeweed mitogen. Molecular studies of the C4 gene region in the patient revealed homozygous deletion of CYP21A-TNXA-RP2-C4B generating total deficiency of C4B and the flanking 5′ region up to C4A, and in the father a missing CYP21A gene. Further investigations are needed to elucidate the relationship between C4B deficiency and susceptibility to infections.

A man with a leg-vein clot and colonic ulcers

A 48-year-old man was admitted to hospital on May 28, 1995, with spasms of lower abdominal pain of variable intensity for 5 weeks, associated with weight loss. He had had a pulmonary embolism after a deep-vein thrombosis 15 years previously. 2 years before admission, he had had pancreatitis of unknown cause. 1 year before admission, colonoscopy had shown a segmental ulcer in the midtransverse colon. He had a segment of colon removed. Histological examination did not establish a cause for the ulcer. He continued to complain of recurrent lower abdominal pain and weight loss. Angiography of his mesenteric arteries was normal. Barium enema radiography of the colon showed a cicatricial stenosis in the mid-transverse colon at the site of the previous resection. This was removed at operation. Histological examination showed a segmental ulcer of unclear cause. After discharge from hospital he still had lower abdominal pain, especially after food. At our institution, physical examination showed he was 180 cm in height and weighed 60 kg. There was paraumbilical tenderness, but no other abnormalities. Repeated stool cultures were negative. Colonoscopy showed a segmental ulcer in the right side of the transverse colon. The ulcer was shallow and 10 cm in diameter. Colonic mucosa at the borders of the ulcer was friable and had petechial haemorrhages. The remainder of the colonic mucosa appeared normal (figure). Ten biopsy specimens were taken. The crypts were of normal height in three specimens and hyperplastic in one. The lamina propria contained normal numbers of lymphocytes and plasma cells and no granulocytes. Six specimens showed granulation tissue and inflammatory cells at the base of an ulcer. The lesion was consistent with an ischaemic ulcer. Histological slides from the second resection of his colon at another hospital showed similar findings. The diagnostic feature was thrombosis of small submucosal and mesenteric vessels, consistent with mesenteric thrombosis. An examination of the clotting system showed resistance to activated protein C, 1 caused

Immunological Evaluation of Children Treated with Antiepileptic Drugs

In order to evaluate cellular and humoral immunity in children who were given carbamazepine (CBZ), sodium valproate (VPA) or phenobarbital (PHB) as monotherapy, we studied 137 children and adolescents suffering from various types of epilepsy and 50 healthy control children. The patients were subdivided according to the type of drug received: in particular, Group 1: 50 (26 female, 24 male) children received only CBZ; their age ranged from 2.3 years to 16.0 years (mean ± SD, 8.1 ± 7.9 years); Group 2: 50 (26 female, 24 male) children received only VPA with age from 2.8 to 15.1 (8.9 ± 7.1) years; Group 3: 37 (20 female, 17 male) children who were given only PHB with age from 2.0 to 13.9 (8.4 ± 7.8) years. 50 sex and age- matched healthy children served as controls. All the patients of groups 1, 2 and 3 were studied before the beginning of antiepileptic drug therapy and after 6, 12 and 18 months of therapy. All plasma levels of AEDs were within the therapeutic range. All children of the three groups had a normal number of lymphocytes per millimeter of blood; also the values of CD3, CD4, CD8, CD20 and CD56 and the serum levels of complement (C3 and C4) were similar to those of healthy controls. The natural killer cell activity of children receiving CBZ showed a significant reduction: this reduction was present after 6 months of therapy (baseline: 45.2%; after 6 months: 32.6%; after 12 months 31.3 %; (all determinations vs baseline:p&lt;0.01) and continued to be present until the end of the study (36.9%; p&lt;0.05). Our data suggest that, in children receiving CBZ, VPA and PHB on monotherapy significant abnormalities of serum immunoglobulin concentrations, serum complement values and lymphocyte subsets are not present. CBZ is shown to have a reducing effect on the natural killer cell activity, but the real role of this abnormality in the immune system of these patients needs more investigation.

Characterization of a noncytopathic HIV-2 strain with unusual effects on CD4 expression.

A new isolate of the human immunodeficiency virus type 2, designated HIV-2UC1, was recovered from an Ivory Coast patient with normal lymphocyte numbers who died with neurologic symptoms. Like some HIV-1 isolates, HIV-2UC1 grows rapidly to high titers in human peripheral blood lymphocytes and macrophages and has a differential ability to productively infect established human cell lines of lymphocytic and monocytic origin. Moreover, infection with this isolate also appears to involve the CD4 antigen. However, unlike other HIV isolates, HIV-2UC1 does not cause cytopathic effects in susceptible T cells nor does it lead to loss of CD4 antigen expression on the cell surface. These results indicate that HIV-2 may be found in individuals with neurologic symptoms and that the biological characteristics of this heterogeneous subgroup can differ from those typical of HIV-1.

Effect of oral colchicine on T cell subsets, monocytes and concanavalin A-induced suppressor cell function in asthmatic patients.

Asthmatic patients have a deficiency of concanavalin A-(Con A) induced suppressor cell function. We tested whether oral colchicine 0.5 mg twice daily for 7 days could correct this immunoregulatory abnormality. Peripheral blood mononuclear cells were incubated with Con A and then suppression of proliferation was measured by coculture of these cells with healthy volunteers' mononuclear cells and phytohaemagglutinin. Sixteen asthmatic patients had significantly (P less than 0.002) decreased Con A-induced suppressor cell function (17.0 +/- 17.2%, mean +/- s.d.) as compared to 13 healthy volunteers (37.9 +/- 14.9%). Oral colchicine significantly (P less than 0.05) increased, though only partially corrected, these 16 asthmatic patients' Con A-induced suppressor cell function (28.1 +/- 14.3%). Asthmatic patients had an increased number of monocytes (691 +/- 289 vs 388 +/- 271/mm3 for normals, P less than 0.01) and a normal number of lymphocytes, Leu 4+ total T cells, Leu 3+ helper/inducer T cells, and Leu 2+ suppressor/cytotoxic T cells as well as a normal Leu 3/Leu 2 ratio. Oral colchicine significantly (P less than 0.005) decreased the number of monocytes (451 +/- 255/mm3) without significantly affecting the number of lymphocytes, Leu 4+, Leu 3+, or Leu 2+ T cells, or the Leu 3/Leu 2 ratio. These results are consistent with the hypothesis that the deficiency of Con A-induced suppressor cell function in asthmatic patients may be due, in part, to an increased number and/or abnormal activity of monocytes. If so, then oral colchicine may have partially corrected the deficiency of Con A-induced suppressor cell function by decreasing the number and/or modulating the activity of monocytes.

Defective natural killing activity but retention of lymphocyte-mediated antibody-dependent cellular cytotoxicity in patients with the X-linked lymphoproliferative syndrome

Cellular mediated immune responses in vitro of six males with X-linked lymphoproliferative syndrome (XLP) were investigated. Impaired natural killing (NK) activity compared to seven controls ( P < 0.001) and interferon-α activation ( P < 0.011) were detected. However, normal numbers of lymphocytes expressing NK-associated antigens (Leu-7 and MO1) and large granular lymphocytes (LGL) were observed in all patients. Normal lymphocyte-mediated antibody-dependent cellular cytotoxicity (ADCC) ( P < 0.531) was found. NK and ADCC activities have been regarded as being mediated by the same subsets of lymphocytes, however, results of this study do not support this hypothesis: lymphocytes with impaired NK but normal ADCC functions ( NK − K + ) were found in males with XLP.

CORRELATIONS BETWEEN PURINE LEVELS, CLINICAL AND.IMMUNOLOGICAL STATUS IN ADA DEFICIENCY: 192

Nine cases of adenosine deaminase (ADA) deficiency have been found amongst fifty infants investigated for immunodeficiency. Prenatal diagnosis identified a further two affected foetuses in six pregnancies at risk. Absence of ADA activity and high dATP levels in foetal blood,with low lymphoid cell numbers and few T-cells, indicated early intrauterine onset.High dATP levels, accompanied by varying degrees of ATP depletion were also found in the red cells of the nine infants. Two late presenters had normal ATP levels, normal lymphocyte numbers and immunoglobulin levels, with some detectable ADA in mononuclear cells (PBMs). dATP was found in PBMs in only one case where heparinised blood contaminated with platelets was used. The novel finding in the two latest cases was the presence of ATP depletion accompanied by dATP accumulation in the platelets but not PBMs from defibrinated blood. This explains the earlier results and questions the possible significance for the immune response.Deoxyadenosine was found in the urine in all cases.S-adenosylhomocysteine was not; adenosine was identified in some. The results suggest that the degree of ATP depletion may reflect the clinical status most closely,but that any therapeutic approaches are likely to be ineffective because of the early toxicity to T-lymphocyte precursors.

Cavitary Pulmonary Sarcoidosis

A 25-year-old woman was initially seen with hilar adenopathy and bilateral cavitary lesions. No cause for these roentgenographic abnormalities other than sarcoidosis could be determined. In contrast to what is usually found in acute sarcoidosis, the bronchoalveolar lavage fluid from this patient contained a normal number of lymphocytes and an increased number of multinucleated giant cells. These findings raise the possibility that patients with acute sarcoidosis and cavitation have an atypical form of this disease. Even though cavitation in acute sarcoidosis is rare, this disorder must be considered in making the differential diagnosis of cavitary lung disease.

Diagnosis of enzootic bovine leukosis: a comparison of haematological and immunodiffusion tests

A total of 657 cattle from three different herds were tested for the presence of specific antibodies against EBL antigens by means of the immunodiffusion test and the results compared with the classification according to the lymphocyte counts. All animals with pathologically raised lymphocyte counts showed a positive immunodiffusion test reaction. In the majority of these both antigens, 'p24' and 'gp', gave positive results; in a smaller number antibodies against the gp antigen only were detected, but never against the p24 antigen only. It is concluded that for field testing programmes the use of the gp antigen is sufficient. In future experiments, however, both antigens should be employed, because the lack of one of them might perhaps prove to be correlated with the future course of the disease. The absence of specific antibodies, together with a normal number of lymphocytes, in young animals should, however, not lead to the conclusion that they are free of the disease.