Refractory systemic lupus erythematosus with chylous effusion successfully treated with sirolimus: a case report and literature review.

Chylous effusion is a rare manifestation of systemic lupus erythematosus (SLE). When it does occur in SLE, it is generally well treated with standard pharmacologic or surgical measures. We present a decade of management in a case of SLE with lung affliction and development of refractory bilateral chylous effusion and pulmonary arterial hypertension (PAH). In the first years, the patient was treated under a Sjogren syndrome diagnose. After few years, her respiratory condition worsened due to chylous effusion and PAH. Immunosuppression therapy (methylprednisolone) was reintroduced, and vasodilator therapy commenced. With this, her cardiac function remained stable, but respiratory function continuously worsened despite several therapy trials with different combinations of immunosuppressant (glucocorticoids, resochin, cyclophosphamide and mycophenolate mofetil). On top of pleural effusion worsening, the patient developed ascites and severe hypoalbuminaemia. Even though albumin loss was stabilized with monthly octreotide applications, the patient remained respiratory insufficient and in need of continuous oxygen therapy. At that point, we decided to introduce sirolimus on top of glucocorticoids and mycophenolate mofetil therapy. Her clinical status, radiological finding, and lung function gradually improved and she became respiratory sufficient at rest. The patient remains in our follow-up and has been stable on given therapy for over 3 years despite overcoming a severe COVID-19 pneumonia in 2021. This case adds to the body of evidence of sirolimus effectiveness in patients with refractory systemic lupus and is, to our best knowledge, the first case to report its successful application in a patient with SLE and refractory chylous effusion.

Human neutrophil antigen-1, -3, -4, and -5 allele and genotype frequencies in the Croatian blood donor population and their clinical significance.

OBJECTIVES: Human neutrophil antigens (HNAs) and antibodies play an important role in allo- and autoimmunity associated with immune neutropenia and transfusion reactions. The aim of this study was to determine the HNA-1, -3, -4 and -5 allele and genotype frequencies in the Croatian blood donor population to assess the role of HNA-1, -3, -4, and -5 alleles in the development of neonatal alloimmune neutropenia and antibody-mediated transfusion-related acute lung injury. MATERIAL AND METHODS: A total of 371 blood samples from unselected healthy blood donors were analyzed. Samples from all 371 donors were genotyped for HNA-1, samples from 160 donors were genotyped for HNA-3, and samples from 142 donors were genotyped for HNA-4 and HNA-5 using the polymerase chain reaction with sequence-specific primers (PCR-SSP) method. RESULTS: The frequencies of the FCGR3B*01, FCGR3B*02 and FCGR3B*03 HNA-1 alleles were 0.393, 0.607 and 0.022, and of the SLC44A2*01 and SLC44A2*02 HNA-3 alleles 0.781 and 0.219, respectively. The frequencies of the ITGAM*01 and ITGAM*02 HNA-4 alleles were 0.796 and 0.204, and of the ITGAL*01 and ITGAL*02 HNA-5 alleles 0.718 and 0.282, respectively. CONCLUSION: These are the first results on the HNA allele and genotype frequencies in the Croatian blood donor population. We observed no deviations from previous reports on Caucasian populations. Determination of the HNA antigen frequencies in the population is important to estimate the risk of alloimmunization to HNA, especially the risk of fetal-maternal incompatibility and alloantibody production by transfusion of the HNA incompatible blood components.

COVID-19 convalescent plasma as long-term therapy in immunodeficient patients?

OBJECTIVES: The patients with hematological malignancies are a vulnerable group to COVID-19, due to the immunodeficiency resulting from the underlying disease and oncological treatment that significantly impair cellular and humoral immunity. Here we report on a beneficial impact of a passive immunotherapy with convalescent plasma to treat a prolonged, active COVID-19 infection in a patient with a history of nasopharyngeal diffuse large B-cell lymphoma treated with the therapy inducing substantial impairment of particularly humoral arm of immune system. The specific aim was to quantify SARS-CoV2 neutralizing antibodies in a patient plasma during the course of therapy. MATERIALS AND METHODS: Besides the standard of care treatment and monitoring, neutralizing antibody titers in patient's serum samples, calibrated according to the First WHO International Standard for anti-SARS-CoV-2 immunoglobulin (human), were quantified in a time-dependent manner. During the immunotherapy period peripheral blood flow cytometry immunophenotyping was conducted to characterize lymphocyte subpopulations. RESULTS: The waves of clinical improvements and worsening coincided with transfused neutralizing antibodies rises and drops in the patient's systemic circulation, proving their contribution in controlling the disease progress. Besides the patient's lack of own humoral immune system, immunophenotyping analysis revealed also the reduced level of helper T-lymphocytes and immune exhaustion of monocytes. CONCLUSION: Therapeutic approach based on convalescent plasma transfusion transformed a prolonged, active COVID-19 infection into a manageable chronic disease.

Warm red blood cell autoantibodies and clinical diagnoses in patients with or without autoimmune hemolysis.

OBJECTIVES: Red blood cell autoantibodies (RBC autoAbs) of IgG class are found in the majority of patients with warm autoimmune hemolytic anemia (wAIHA) but sometimes also during the pretransfusion testing of patients with different diagnoses but without hemolysis. The aim of the study was to identify the main differences between these two groups of patients according to age, gender, subclass and titer of IgG RBC autoAbs and diagnosis. MATERIAL AND METHODS: In the 9-year retrospective study, data were collected from records of 291 patients with IgG RBC autoAbs detected by gel technique, from which 111 with wAIHA. RESULTS: More than 85% of patients in both groups were over 40 years old, with male to female ratio 1:1.9 in wAIHA vs 1:1.3 in patients without hemolysis (P=0.0916). The main characteristics of patients with wAIHA vs patients without hemolysis were: IgG only 38% vs 70%, IgG+Complement 62% vs 30%, total IgG1 79% vs 55%, IgG1+IgG3 35% vs 11%, titer of 100 for IgG1+IgG3 17% vs 3% (P<0.0001), respectively, while titer of 100 for IgG1 18% vs 9% (P=0.0241). The underlying diagnosis in wAIHA vs patients without hemolysis: hematologic disorders 41% vs 22% (P=0.0006), autoimmune disorders 12% vs 13% (P=0.8033), solid tumors 5% vs 14% (P=0.0154) and surgery procedures 6% vs 26% (P<0.0001). CONCLUSION: We observed more wAIHA patients with high titer of IgG1 and high prevalence of IgG1+IgG3 and consider that patients without hemolysis having identical results might be interesting to find out how they are protected from damage by RBC autoAbs.

Estimation of the hepatitis E assay-dependent seroprevalence among Croatian blood donors.

BACKGROUND: Seroprevalence of hepatitis E virus (HEV) in blood donors presenting to the Croatian Institute of Transfusion Medicine was assessed with 4 available tests (3 ELISA tests and 1 immunoblot (IB) test). MATERIALS AND METHODS: In October and November 2014, a total of 1,036 serum samples of blood donors were collected for the study. Samples were primarily tested for total HEV antibodies by Dia.Pro HEV Ab test (a). All reactive samples were tested by ELISA tests: Dia.Pro HEV IgG (b) and IgM (c), Mikrogen recomWell HEV IgG_old (d) and IgM_old (e), recomWell HEV IgG_new (f) and IgM_new (g), and IB Mikrogen recomLine HEV IgG (h) and IgM (i). HEV IgM reactive samples also positive by the IB were further tested for HEV RNA. RESULTS: There were 21.5% of samples reactive for total HEV antibodies (a). Seroprevalence of HEV IgG according to the b, d, f and h tests was 20.2%, 9.6%, 18.1% and 17.8%, respectively. Seroprevalence of HEV IgM according to the c, e, g and i tests was 4.4%, 1.5%, 2.0% and 1.7%, respectively. Out of 46 HEV IgM (Dia.Pro HEV IgM) positive samples, 18 (39.1%) were also positive by IB. HEV RNA was not detected in any of those samples. There was a significant association between age and HEV seroprevalence (P<0.001). CONCLUSION: Different HEV antibody detection assays showed a high HEV IgG seroprevalence in Croatian blood donors. Among HEV IgG and HEV IgM positive samples HEV RNA was not detected.

Lung Abscess: An Early Complication of Lung Transplantation in a Patient with Cystic Fibrosis.

A 22-year-old woman with cystic fibrosis (CF) developed lung abscess, as a rare complication caused by multidrug-resistant (MDR) Acinetobacter baumannii infection, after lung transplantation (LT). After 6 months of long-term antibiotic therapy, the abscess was successfully eliminated. In reviewed published literature, no previous report was found describing this kind of complication caused by MDR A. baumannii in post-LT patient with CF. In our experience, lung abscess in LT recipients with CF can be successfully treated with prolonged antibiotic therapy.

Early onset of nontuberculous mycobacterial pulmonary disease contributes to the lethal outcome in lung transplant recipients: report of two cases and review of the literature.

Lung transplant (LuTx) recipients represent a population at risk of nontuberculous mycobacterial pulmonary disease (NTM-PD). Yet the risk factors, the timing of NTM-PD after transplantation, and the association with allograft dysfunction all remain poorly defined. We report 2 cases of early-onset NTM-PD and review the literature, focusing on NTM-PD in LuTx recipients not colonized with NTM prior to transplantation. In addition, we summarize the main characteristics and differences between early- and late-onset disease.

SUCCESSFUL TREATMENT OF PULMONARY AND LYMPHATIC MANIFESTATIONS OF LYMPHANGIOLEIOMYOMATOSIS WITH SIROLIMUS.

Lymphangioleiomyomatosis (LAM) is a rare, progressive, diffuse cystic lung disease predominantly affecting women of child bearing age. Recently treatment with sirolimus was shown to stabilize lung function decline and improve quality of life in patients with LAM. We treated three premenopausal women suffering from LAM manifesting as diffuse cystic lung disease, chylous effusions, and lymphangioleioyomas with sirolimus (1-3 mg a day; sirolimus trough levels 2.9-8.5 ng/ml). All three patients had a remarkable response to sirolimus, with resolution of effusions, improvement in lung function and shrinking of abdominal lymphangioleiomyomas. Our case series further complements the literature in that sirolimus is a safe and effective treatment for LAM and its lymphatic manifestations.

Solitary pulmonary amyloidoma mimicking lung cancer on 18F-FDG PET-CT scan in systemic lupus erythematosus patient.

Localized amyloid deposits (tumoral amyloidosis or amyloidoma) are uncommon form of amyloidosis and nodular pulmonary amyloidomas are rarely found. This incidental finding can mimic a bronchopulmonary neoplasm and may occur secondarily to an infectious, inflammatory or lymphoproliferative disease. We report a case of a 62-year-old female with long-standing systemic lupus erythematosus (SLE) with low compliance who presented with radiologically-verified solitary pulmonary nodule. Work-up included positron emission tomography-computed tomography (PET-CT) scan, which revealed hypermetabolic uptake of (18)F-fluorodeoxyglucose, and lobectomy was performed. Staining of the tissue was positive for Congo red and was green birefringent under polarized light. Immunohistochemical methods excluded lymphoproliferative disease and confirmed amyloidoma. SLE was controlled with antimalarials and glucocorticoids. Pulmonary amyloidoma should be considered in the differential diagnosis of solitary lung nodules.

Bacterial contamination of blood products at the Croatian Institute of Transfusion Medicine: results of eleven-year monitoring.

OBJECTIVES: The aim of this study is to present the results and experiences of the Croatian Institute of Transfusion Medicine (CITM) in blood product testing for the presence of bacterial contamination. This is the first study analysing the results of bacterial testing of blood products in Croatia. METHODS: Results of monitoring blood products for the presence of bacterial contamination during an 11-year period (2000-2010) were retrospectively analysed. As universal screening of platelet concentrates for bacterial contamination is not mandatory in Croatia, the results presented refer to the products tested within the frame of statistical process control. RESULTS: A total of 23,130 blood products were tested during the study period. There were 122 (0·53%) initially positive and 41 (0·18%) confirmed positive blood products, whereas suspicion of bacterial contamination could be neither confirmed nor ruled out in 8 (0·03%) blood products. While the frequency of bacterial contamination of plasma products was very low (0·03%), there was no statistically significant difference between bacterial contamination of platelet concentrates (0·26%) and RBC concentrates (0·20%). There were 73 (0·32%) false-positive blood products, with nearly equal proportion of causes related to laboratory contamination (n = 34; 0·15%) and those related to the testing system (n = 39; 0·17%). CONCLUSION: The results obtained in the study did not differ significantly from literature data. A number of measures to reduce the risk of bacterial contamination of blood products have been implemented at CITM. The introduction of universal screening of platelet concentrates for the presence of bacterial contamination should be taken into consideration.