Biomedical subjects

W E Fibbe

Publications and source records attributed to W E Fibbe.

At least 55 records · Page 3Linked to original sources

PubMed1998

The early phase of engraftment after murine blood cell transplantation is mediated by hematopoietic stem cells.

Blood cells transplantation is largely replacing bone marrow transplantation because engraftment is more rapid. This accelerated engraftment is thought to be mediated by relatively mature committed hematopoietic progenitor cells. Herein, we have used a modified rhodamine (Rho) staining procedure to identify and purify Rho+/++ (dull/bright) and Rho- (negative) subpopulations of hematopoietic progenitor cells in murine cytokine-mobilized blood. The Rho+/++ cell population contained > 99% of committed progenitor cells with in vitro colony-forming ability. The Rho- cell population contained the majority of hematopoietic stem cells with in vivo marrow repopulating ability. The rate of hematopoietic reconstitution was identical in recipients of grafts containing only purified Rho- stem cells or purified Rho- stem cells in combination with large numbers of Rho+/++ committed progenitor cells. In contrast, transplantation of 3-fold more hematopoietic stem cells resulted in accelerated reconstitution, indicating that the reconstitution rate was determined by the absolute numbers of Rho- stem cells in the graft. In addition, we observed a 5- to 8-fold reduced frequency of the subset of hematopoietic stem cells with long-term repopulating ability in cytokine-mobilized blood in comparison to steady-state bone marrow. Our results indicate that hematopoietic stem cells and not committed progenitor cells mediate early hematopoietic reconstitution after blood cell transplantation and that relative to bone marrow, the frequency of stem cells with long-term repopulating ability is reduced in mobilized blood.

Animals↗

PubMed1998

The molecular basis of leukocytosis.

The function of any known gene is often found by DNA or protein homology scanning. Conversely, it is equally rewarding to search for the genetic basis behind a known function. Here, Ghislain Opdenakker and colleagues examine the known and possible novel genes and molecular events underlying the phenomenon of leukocytosis, one of the most common clinical manifestations of inflammatory problems.

Humans↗

PubMed1998

Unrelated donor bone marrow transplantation in Fanconi anaemia: the Leiden experience.

Fanconi anaemia (FA) is an accepted indication for treatment with allogeneic HLA-identical BMT. Most patients, however, lack a suitable HLA-identical donor. In our centre, six FA patients were transplanted with a matched unrelated donor. Due to hypersensitivity to DNA cross-linking agents, a low-dose cyclophosphamide (CY) and thoraco-abdominal irradiation (TAI) regimen is recommended for conditioning in FA. We added Ara-C upfront and anti-T cell antibodies to enhance engraftment and to prevent GVHD, in combination with T cell depletion in four out of six of the first transplants. One patient did not engraft. In three patients rejection was observed. In three of these four patients a second BMT, using full bone marrow grafts, resulted in successful engraftment. The other patient died before a second BMT could be performed. The incidence and severity of acute GVHD was low: only one patient with grade III acute GVHD was seen. Two out of four surviving patients suffered from chronic GVHD. Four patients survived (median survival time 43 months after BMT), three with good and one with acceptable quality of life. Two patients died, one patient due to adenoviral reactivation with multi-organ failure, and one due to sepsis complicated by ARDS. In conclusion, MUD BMT is feasible in FA patients with bone marrow failure in whom no HLA-identical sibling donor is available. In our study group, the major problem was graft rejection, despite the administration of a combination of graft enhancing anti-T cell antibodies. Multicentre studies are needed to determine a more intensive, but still tolerable, conditioning regimen.

Adult↗

PubMed1998

Effects of thrombopoietin on the proliferation and differentiation of primitive and mature haemopoietic progenitor cells in cord blood.

Thrombopoietin (TPO) is considered to be the primary growth factor for regulating megakaryopoiesis and thrombopoiesis. In this study we investigated the in vitro effect of TPO on relatively immature and mature CD34+ progenitor cells in cord blood. Cells were cultured in both liquid and semi-solid cultures containing 50 ng/ml TPO. The CD34+/CD45RA- and CD34+/CD38- subfractions in cord blood were both enriched for megakaryocyte progenitors as determined in a semisolid CFU-meg assay. Progenitor cells derived from the CD34+/CD45RA- and CD34+/CD38- subfractions showed high proliferative capacity in liquid cultures. We observed a mean 19-fold expansion of the total CD34+ cell fraction, whereas in the CD34+/CD45RA- and CD34+/CD38- subfractions the mean expansion was 23- and 50-fold respectively. The expansion of the immature progenitor cell subfractions resulted in a highly purified megakaryocyte suspension containing > 80% megakaryocytes after 14 d in culture. However, these expanded megakaryocytes remained in a diploid (2N) and tetraploid (4N) state. Maturation could not be further induced by low concentration of TPO (0.1 ng/ml). The majority of the cells were 2N (80%) and 4N (15%) and only 5% of the cells had a ploidy of more than 4N. These results indicate that megakaryocyte progenitor cells in cord blood residing in the immature stem cell fraction exhibit a high proliferative capacity when cultured in the presence of TPO as the single growth factor, without maturation to hyperploid megakaryocytes.

ADP-ribosyl Cyclase↗

PubMed1998

A retrospective Dutch study comparing T cell-depleted allogeneic blood stem cell transplantation vs T cell-depleted allogeneic bone marrow transplantation.

Retrospectively, a cohort of 43 hematological patients receiving an allogeneic T cell-depleted (TCD)-PBSCT between 1994 and 1997, was compared to a cohort of 435 patients, who received an allogeneic TCD-BMT between 1990 and 1996. Both cohorts were comparable with respect to diagnosis, risk status, age and sex. PB grafts contained four to five times more hematopoietic progenitor cells and T cells as compared to BM grafts. T cell depletion was performed by either elutriation, CD34 selection, E-rosetting, or Campath serotherapy. Conditioning was cyclophosphamide/TBI in the majority of patients of both cohorts. All patients received cyclosporin A as GVHD prophylaxis until day 90 post-transplant. Engraftment was significantly faster in the PBPCT cohort with a median time to neutrophil recovery (>0.5 x 10(9)/l) of 16 vs 21 days in the BMT cohort (P = 0.0009). Platelet recovery to 50 x 10(9)/l was 16 vs 34 days for the PB and BM cohort respectively (P < 0.0001). A median percentage of 76% of BMT patients recovered to 50 within 100 days post-BMT vs 91% of patients receiving a PB graft. The incidence of acute GVHD grades II, III and IV was similar in both cohorts. In contrast, the probability of developing chronic GVHD was 21% in the BM cohort vs 37% in the PB cohort. Relapse incidence was reduced in the PB cohort (9 vs 29%), while treatment-related mortality was not different for both cohorts. These favorable results require confirmation by a prospective randomized trial, which is currently being performed by several European centers.

Adolescent↗

PubMed1997

[High-dose chemotherapy followed by hematopoietic stem cell transplantation as therapy for systemic rheumatic autoimmune diseases].

Remissions of autoimmune diseases can be accomplished in animals by myeloablative chemotherapy followed by allogeneic or autologous bone marrow transplantation. Remissions of autoimmune diseases have been reported in patients with concomitant malignancies for which they were treated with myeloablative chemotherapy followed by stem cell transplantation. Survival of patients with systemic rheumatic autoimmune disease is reduced. Since transplantation related mortality after autologous stem cell transplantation is less than 5%, this treatment becomes a possibility for patients with severe systemic rheumatic autoimmune disease, such as systemic sclerosis.

Adult↗

PubMed1997

Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins.

The mdr1-type P-glycoproteins (P-gps) confer multidrug resistance to cancer cells by active extrusion of a wide range of drugs from the cell. To study their physiological roles, we have generated mice genetically deficient in the mdr1b gene [mdr1b (-/-) mice] and in both the mdr1a and mdr1b genes [mdr1a/1b (-/-) mice]. In spite of the host of functions speculatively attributed to the mdrl-type P-gps, we found no physiological abnormalities in either strain. Viability, fertility, and a range of histological, hematological, serum-chemical, and immunological parameters were not abnormal in mdr1a/1b (-/-) mice. The high level of mdrlb P-gp normally present in the pregnant uterus did not protect fetuses from a drug (digoxin) in the bloodstream of the mother, although the protein did reduce drug accumulation in the adrenal gland and ovaries. Pharmacologically, mdr1a/1b (-/-) mice behaved similarly to the previously analyzed mdr1a (-/-) mice, displaying, for instance, increased brain penetration and reduced elimination of digoxin. However, both mdr1a and mdr1b P-gps contributed to the extrusion of rhodamine from hematopoietic progenitor cells, suggesting a potential role for the endogenous mdr1-type P-gps in protection of bone marrow against cytotoxic anticancer drugs. This, and the normal viability of mdr1a/1b (-/-) mice, has implications for the use of P-gp-blocking agents in cancer and other chemotherapy. mdr1a/1b (-/-) mice should provide a useful model system to further test the pharmacological roles of the drug-transporting P-gps and to analyze the specificity and effectivity of P-gp-blocking drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

Leukemia inhibitory factor induces in vivo expansion of bone marrow progenitor cells that accelerate hematopoietic reconstitution but do not enhance radioprotection in lethally irradiated mice.

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine with distinct hematopoietic activities. In vivo treatment of mice with recombinant murine LIF induces thrombocytosis and increases the number of hematopoietic progenitor cells (HPCs) in spleen and bone marrow (BM). In this study, we applied LIF to expand HPCs in vivo prior to syngeneic BM transplantation. BALB/c donor mice were treated with recombinant human LIF at a dose of 2.5 microg/day s.c. for seven days. This resulted in a 1.6-fold increment in platelet counts from 941 to 1,470 x 10(9)/l (mean, n = 20). Mean spleen weight increased from 120 mg to 160 mg (n = 5). The total numbers of HPCs in the spleen as well as in the BM, as assessed in a CFU-GM (colony forming unit-granulocyte-macrophage) assay, were significantly higher in LIF-treated donors than in saline-treated controls (30.1 +/- 14.5 versus 7.4 +/- 5.3 x 10(3) per spleen; mean +/- SD, n = 22,p < 0.001 and 74.4 +/- 17.1 versus 55.3 +/- 16.1 x 10(3) per femur, p < 0.001). Recipient mice were lethally (8.5 Gy) irradiated and transplanted with 3 x 10(5) BM cells derived from LIF- or saline-treated donors. Hematopoietic reconstitution was monitored by tail bleeding at three-day intervals. Platelet and WBC nadir counts in control animals were reached at day 9 (31 +/- 25 x 10(9)/l for platelets and 0.40 +/- 0.10 x 10(9)/l for WBC; mean +/- SD, n = 29 per treatment group); in animals transplanted with LIF-treated BM cells, these counts were 44 +/- 25 x 10(9)/l for platelets, p < 0.05 and 0.60 +/- 0.38 x 10(9)/l for WBC, p < 0.01. In addition, platelet reconstitution was faster in recipients of LIF-treated BM cells (226 +/- 118 versus 126 +/- 62 x 10(9)/l at day 12 and 633 +/- 174 versus 434 +/- 180 x 10(9)/l at day 15, p < 0.001). Similarly, the reconstitution of WBC was also significantly enhanced. The radioprotection rate of lethally irradiated recipients with increasing cell doses of BM cells derived from LIF-treated donors was higher at all cell doses tested then of control animals, but did not reach statistical significance. These results show that in vivo treatment with LIF expands the number of committed progenitor cells and BM repopulating cells that accelerate short-term hematopoietic reconstitution without increasing radioprotection. Our data do not support a major role for LIF as a single factor inducing expansion of hematopoietic stem cells in vivo.

Animals↗

PubMed1997

Differential short-term and long-term repopulating ability of stem cell subsets in mice.

Hematopoietic reconsitution after transplantation requires the presence of cells with early and late repopulating ability. To determine the contribution of relatively immature and mature hematopoietic progenitor cells in engraftment, we used a modified rhodamine staining procedure to purify populations of rhodamine 123 (Rho)bright, Rhodull and Rho- cells from mouse steady-state bone marrow. Following transplantation of these subsets of stem cells in lethally irradiated mice, marrow repopulating cells were mainly present in the small fraction of Rho- cells, indicating that hematopoietic stem cells have a relatively high expression of P-glycoprotein. Similar cell populations could be purified from cytokine-mobilized blood following treatment with cyclophosphamide and G-CSF. The Rho- cell population contained the majority of hematopoietic stem cells with in vivo marrow repopulating ability. In methylcellulose colony assays, the majority of the committed progenitor cells were present in Rhodull and Rhobright fractions. These results indicate that relatively primitive populations of hematopoietic stem cells that lack colony-forming capacity in vitro mediate the early phase of engraftment following syngeneic stem cell transplantation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

Problems and possible solutions in finding an unrelated bone marrow donor. Results of consecutive searches for 240 Dutch patients.

To evaluate the efficiency of our protocol for finding an HLA matched unrelated bone marrow donor, search results obtained between 1990 and 1995 for 240 Dutch patients were analyzed. The percentage of patients for whom, according to information given by the registries, a fully split-HLA antigen matched donor is available, increased from 24% in 1990 to over 70% in 1995. As a result the percentage of patients transplanted rose from about 24% in 1990-1991 to 44% in 1994-1995. The median time between the start of the search and transplantation was about 6 months. The systematic use of Bone Marrow Donors Worldwide (BMDW) which comprises the HLA groups of all volunteer bone marrow donors in Europe, Israel, South Africa, North America, Canada, India, Australia and New Zealand has been essential in this context. While searching for a suitable donor several problems were encountered such as unavailability of donors (12%) and discordant typing results (8%; range < 1% to > 25%). Thus it is advisable to select several donors for a patient. For 86% of patients with at least one HLA identical donor on the serological level for HLA-A,-B,-DR,-DQ, an HLA-DRB1/3/4/5, and -DQB1 identical donor could be identified. As expected, patients with two frequent haplotypes in strong linkage disequilibrium had the best chance of obtaining an HLA matched donor. Unexpectedly, patients with only one such haplotype had an almost similar chance. It could be calculated that HLA-DR typing of HLA-A,-B identical donors was rarely cost-effective after 1992. Only 12 of the 75 transplanted patients (16%) typeable at DNA level for class II, turned out to be completely matched for HLA-A,-B,-C,-DRB1/3/4/5,-DQB1,-DPB1 and had a negative MLC test. In the group of patients transplanted with a fully matched donor and for whom a CTLp test was performed, only 7% (4/54) of the tests were negative. Search results for patients of non-European origin were dismal, with only four of 26 patients referred being transplanted. In summary, of the 240 patients for whom the Europdonor office searched for a donor, about one-third were transplanted, one-third had a potential donor but did not reach transplantation, while for the remaining one-third of patients no suitable donor could be found.

Adult↗

PubMed1997

T cells selectively infiltrate bone marrow areas with residual haemopoiesis of patients with acquired aplastic anaemia.

Aplastic anaemia (AA) is characterized by pancytopenia and bone marrow (BM) hypocellularity. In some patients AA may be mediated by T cells. To localize inflammatory cell infiltrates, we carried out a quantitative immunohistochemical analysis of BM biopsies of AA patients. In five out of eight biopsies, significantly higher numbers T cells were found in the areas with residual haemopoiesis (RH). The significantly increased numbers of CD3+ T cells in areas with RH supports the hypothesis of a site-directed infiltration and/or a local proliferation of T cells in the BM of patients with AA.

Anemia, Aplastic↗

PubMed1997

Analysis of T-cell clonality in bone marrow of patients with acquired aplastic anaemia.

Acquired aplastic anaemia (AA) represents a state of bone marrow (BM) failure which is characterized by BM hypocellularity and pancytopenia. It has been hypothesized that in some AA patients, bone marrow failure is secondary to the targeted destruction of haemopoietic stem cells by autoreactive T cells. The response of T cells to antigenic stimulation has been shown, in a number of animal models and in autoimmune diseases, to result in the (oligo)clonal expansion of positively reacting T cells. For this reason, we studied the utilization of 24 T-cell receptor-variable gene segments (TCRBV) and the clonality in BM aspirates and peripheral blood (PB) of seven AA patients. BM from transplant donors served as controls. Determination of TCRBV gene segment usage revealed no significant differences between patients and controls. Clonality within each family was analysed by single-strand conformation polymorphism (SSCP) analysis. Clonal and clonally predominant bands were seen in BM of three AA patients in five to eight TCRBV families. Clonal rearrangements were encountered less often in BM of control subjects. In conclusion, our results suggest an antigen-driven T-cell response in the BM of predominantly AA patients resulting in oligoclonal T-cell outgrowth.

Adolescent↗

PubMed1997

Treatment of T-cell prolymphocytic leukemia with human CD52 antibody.

PURPOSE: T-prolymphocytic leukemia (T-PLL) is an aggressive malignancy of mature T cells refractory to conventional chemotherapy, with a median survival duration of 7.5 months. We report here promising results with the use of a genetically reshaped human CD52 antibody, CAMPATH-1H. PATIENTS AND METHODS: Fifteen patients with T-PLL, most of whom had received the purine analog deoxycoformycin (DCF), were treated with CAMPATH-1H. Results were compared with those of 25 patients treated with DCF. RESULTS: Major responses occurred in 11 patients (73%) treated with CAMPATH-1H compared with 40% with DCF. Complete remissions (CRs) were documented in nine (60%) of the CAMPATH-1H cases and only three (12%) were obtained with DCF. CRs with CAMPATH-1H were durable, and re-treatment with the antibody resulted in second CRs in three relapsed patients. Two of them were successfully autografted with peripheral-blood and bone marrow stem cells collected during the first CR. Apart from first-dose reactions, infusions of CAMPATH-1H were well tolerated. However, two responding patients developed severe bone marrow aplasia that was fatal in one; the second remained moderately pancytopenic 21 weeks after stopping CAMPATH-1H therapy. The cause of this adverse effect is unknown. CONCLUSION: CAMPATH-1H is an effective agent in T-PLL and represents a significant improvement over other types of therapy. However, CAMPATH-1H alone is not sufficient for long-term remissions, and the role of autologous stem-cell transplantation needs further investigation.

Adult↗

PubMed1996

Colony growth of human hematopoietic progenitor cells in the absence of serum is supported by a proteinase inhibitor identified as antileukoproteinase.

Serum contains many growth factors and nutrients that stimulate colony formation of hematopoietic progenitor cells (HPC) in semisolid cultures. In the absence of serum, no proliferation of HPCs could be obtained in semisolid medium cultures of partially purified bone marrow cells in the presence of multiple hematopoietic growth factors, insulin, cholesterol, and purified clinical-grade human albumin. This appeared to be due to a suppressive activity induced by monocyte- and T lymphocyte-depleted accessory cells on CD34+ HPCs. Serum-free conditioned medium from the bladder carcinoma cellline 5637 could replace serum to support the growth of HPCs in these cultures. After gel filtration and reverse-phase high-performance liquid chromatography of 5637 supernatants, this activity could be attributed to a 15-kD protein that was further identified by NH2-terminal sequence analysis as the serine proteinase inhibitor antileukoproteinase (ALP). The growth-supportive activity from the 5637 conditioned medium and the (partially) purified fractions could be completely neutralized by a polyclonal rabbit IgG antibody against human ALP (huALP). Similar supportive effects on the growth of HPC could be obtained in the presence of recombinant huALP. We demonstrated that the COOH-terminal domain of ALP containing the proteinase inhibitory activity was responsible for this effect. alpha-1 proteinase inhibitor was capable of similar support of in vitro HPC growth. These results illustrate that proteinase inhibitors play an important role in the in vitro growth of hematopoietic cells by the neutralization of proteinases produced by bone marrow accessory cells. This may be of particular relevance for in vitro expansion of human hematopoietic stem cells in serum-free media.

Amino Acid Sequence↗

PubMed1996

A novel murine cathelin-like protein expressed in bone marrow.

A novel cDNA encoding a putative secreted protein was isolated from murine bone marrow. The encoded protein named MCLP (murine cathelin-like protein) was found to be highly homologous to the pig cathelin, and to four neutrophil antimicrobial polypeptides: CAP 18, indolicidin, Bac 5 and FALL-39. Secondary structure prediction studies identified a highly cationic region in the C-terminal part of prepro-MCLP with a tendency to adopt an amphipathic alpha-helical conformation, as observed in many antimicrobial peptides. However, no antibacterial activity was observed with the synthetic peptide corresponding to this region of MCLP.

Amino Acid Sequence↗

PubMed1996

Rapid mobilization of hematopoietic progenitor cells in rhesus monkeys by a single intravenous injection of interleukin-8.

Interleukin-8 (IL-8) is a chemoattractant cytokine involved in chemotaxis and activation of neutrophils. Because in vivo administration of IL-8 induces mobilization of hematopoietic stem cells in mice, we assessed the mobilizing properties of IL-8 in rhesus monkeys. Recombinant human IL-8 was administered as a single intravenous injection at doses of 10, 30, and 100 micrograms/kg to rhesus monkeys (age, 2 to 3 years; weight, 2.5 to 4.5 kg). Venous blood samples were obtained at time intervals ranging from 1 to 480 minutes after IL-8 administration. Cell counts, colony-forming unit-Mix assays, and fluorescence-activated cell sorter analysis were performed. Plasma was harvested to assess IL-8 levels. A time-controlled bolus intravenous injection of 100 micrograms IL-8 per kilogram of body weight resulted in peak IL-8 plasma levels up to 5 micrograms/mL. The calculated half-time life of free IL-8 was 9.9 +/- 2.2 minutes. IL-8 injection resulted in instant neutropenia that was due to pulmonary sequestration, as shown using 99mTc-labeled leukocytes. Within 30 minutes after IL-8 injection, neutrophilia developed with counts up to 10-fold greater than baseline levels. The numbers of hematopoietic progenitor cells (HPCs) increased from 45 +/- 48/mL to 1,382 +/- 599/mL of blood at 30 minutes after injection of 100 micrograms IL-8 per kilogram of bodyweight (mean +/- SD, n = 8). Individual animals showed 10- to 100-fold increase in numbers of circulating HPCs that returned to almost pretreatment values (92 +/- 52 CFU/mL) at 240 minutes after the injection of IL-8. Immunophenotyping showed no significant changes in lymphocyte (sub)populations. A second bolus injection of IL-8 with an interval of 72 hours resulted in similar numbers of mobilized stem cells as observed after the first injection, showing that no tachyphylaxis had occurred. We conclude that IL-8 induces mobilization of HPCs from the bone marrow of rhesus monkeys in a rapid and reproducible fashion. Therefore, IL-8 may be a potentially useful cytokine in the setting of blood stem cell transplantation.

Animals↗

PubMed1996

Accelerated platelet reconstitution following transplantation of bone marrow cells derived from IL-6-treated donor mice.

We transplanted bone marrow cells derived from normal donor mice treated with IL-6 to study the effect on the hematopoietic recovery of lethally irradiated (8.5 Gy) recipients. Male Balb/C mice were treated for 7 days by continuous infusion of IL-6 (10 micrograms/day). Not only did these donor mice have increased numbers of circulating platelets as was previously shown; the numbers of circulating progenitor cells also increased more than 25-fold. Transplantation of nucleated bone marrow cells derived from these donor mice into lethally irradiated female recipients resulted in increased platelet nadir counts in comparison to recipients of normal bone marrow cells and similar to nadir counts of recipients of normal donor bone marrow treated with IL-6 for 7 days after transplantation. Combination of transplantation of bone marrow derived from IL-6 treated donors with post-transplantation treatment of the recipients with IL-6 resulted in a further increase in nadir counts, although it did not cause a further acceleration of platelet reconstitution. We conclude that transplantation of bone marrow cells modified in vivo by IL-6 results in significantly accelerated reconstitution of platelets, to a degree similar to that observed following treatment with IL-6 after transplantation.

Animals↗

PubMed1996

Aplastic anaemia patients with clonal X-chromosome inactivation pattern in haemopoietic cells exhibit polyclonal TCRgamma and IgH gene rearrangements.

Previously, we reported that 13/18 (72%) female patients with aplastic anaemia (AA) exhibited a clonal X-chromosome inactivation (XCI) pattern in all haemopoietic lineages. To study the consequences of a clonal haemopoiesis for the randomness of immunoreceptor rearrangements in lymphocytes we determined clonality of T-cell receptor gamma (TCRgamma) and immunoglobulin heavy chain (IgH) gene rearrangements in purified cell fractions. Peripheral blood granulocytes, monocytes, and B and T lymphocytes from 18 female patients in remission from AA were studied by PCR for randomness of XCI and rearrangement at the IgH and TCRgamma locus. 13 patients were informative at the phosphoglycerate kinase-1 (PGK1) and monoamine oxidase A (MAOA) loci. Five of them displayed an clonal XCI pattern in all lineages studied and one patient had a clonal XCI in all lineages, except the T cells. In three cases skin biopsies were also available, exhibiting a polyclonal pattern in two of them, and a reversed skewed pattern in the third. Analysis of the rearrangement patterns at the immunoreceptor loci revealed a polyclonal ladder of bands, irrespective of XCI status in the lymphocyte populations. These results demonstrated that in AA a clonal XCI pattern of the lymphoid compartment is compatible with a polyclonal immunoreceptor rearrangement pattern.

Adult↗