Participants enrolled in any clinical study receiving experimental treatments for PNH (evaluated at baseline).Participant unable to read and write in Italian language and to autonomously fill in questionnaires and scales (evaluated at enrolment).Known pregnant or breastfeeding participant (evaluated at baseline).History of hematopoietic stem cell transplantation (evaluated at baseline).Signed written informed and privacy consent prior to study participation.Vaccinated against Neisseria meningitidis (according to Summary of Product Characteristics) Participant already assigned to ravulizumab treatment as a specific therapeutic strategy within the current routine clinical practice (this decision has to be made independently and before the enrolment of the participant in the study).Clinically stable after having been treated with eculizumab for at least the past 6 months.
Documented diagnoses of PNH confirmed by high-sensitivity flow cytometry evaluation of red blood cells and white blood cells with granulocyte or monocyte clone size of ≥ 5%.Hemolysis with clinical symptom(s) indicative of high disease activity.Why Should I Register and Submit Results?.To the best of our knowledge, diminished expression of CD55 and/or CD59 was not reported before in SLE patients with isolated neutropenia in the absence of PNH. Our patient also had concomitant pulmonary embolism. We think that the diminished expression of complement regulatory proteins in the presented patient might be secondary to SLE-derived autoantibodies, which might lead to complement-mediated cell (neutrophil) lysis and might have contributed to the development of neutropenia. Our patient had neutropenia with a normal lymphocyte count and did not seem to have PNH as she had no discrete PNH clone, despite diminished expression of CD59 on erythrocytes and CD55-CD59 expression on neutrophils. However, diminished expression of CD55 and/or CD59 leading to enhanced susceptibility to complement-mediated lysis might also have caused lymphopenia. Antibodies against lymphocytes are claimed to cause lymphopenia via mechanisms including antibody-dependent cellular cytotoxicity, opsonization, surface receptor blockage, or apoptosis. Diminished expression of CD55 and/or CD59 was previously reported in SLE patients with lymphopenia and hemolytic anemia. PNH is characterized by the deficiency of glycosyl phosphatidylinositol-anchored proteins CD55 and CD59, leading to increased susceptibility to complement-mediated lysis of erythrocytes, leukocytes, and platelets. Informed consent was obtained.ĭiminished expression of CD55 and CD59 on patient neutrophils. The expressions of CD59 and CD55 on lymphocytes were normal. Flow cytometry analysis showed diminished expression of CD59 and CD55 in the neutrophils and erythrocytes in the absence of a discrete clone ( Figures 1a and and1b). Proteins C and S and antithrombin III antigens were all within the reference range. Genetic mutations for factor V Leiden and the prothrombin gene were negative. Tests for antiphospholipid syndrome including lupus anticoagulants, β2-glycoprotein I antibodies, and anticardiolipin and antiphospholipid antibodies were all negative. Immunological tests revealed positive antinuclear antibodies (3 positive, thin granular, spotted) and anti-dsDNA at a level of 587 IU/mL. Serum biochemistries were within normal limits. Blood cell counts revealed neutropenia with a white blood cell count of 2.32x109/L, neutrophil count of 0.94x109/L, lymphocyte count of 0.93x109/L, hemoglobin of 137 g/L, and platelet count of 254x109/L. After the diagnosis of SLE, steroids and hydroxychloroquine were begun, which she stopped taking on her own. She also had a previous history of deep venous thrombosis of the left lower extremity while on oral contraceptives 2 years prior to the diagnosis of SLE. She was treated with heparin, which was followed by warfarin. Ī 30-year-old female with a history of SLE was diagnosed with pulmonary artery embolism after being admitted to the hospital with sudden-onset dyspnea. However, diminished expression of CD55 and CD59 on red blood cells and lymphocytes has been demonstrated in SLE patients in the absence of PNH. The association of systemic lupus erythematosus (SLE) and paroxysmal nocturnal hemoglobinuria (PNH) has been rarely reported.
0 kommentar(er)
