Successful Treatment of Anemia With Anaplastic and Microangiopathic Characteristics in a Kidney Transplant Recipient With Parvovirus B19 Infection: A Case Report.

BACKGROUND: The prevalence of parvovirus B19 infection in renal transplantation ranges from 2% to 30%. The age and immune status of the patient influence the severity of the clinical picture. A diagnosis is made by taking as evidence the giant proerythroblasts on a bone marrow sample and the parvovirus B19 viral replication with a polymerase chain reaction (PCR) technique at the blood level. Clinically, parvovirus B19 may appear with fever and severe anemia, which can be followed by pancytopenia and thrombotic microangiopathy in some cases. The literature reports a graft dysfunction rate ranging from 10% to 36%. An infection relapse may happen in 30% of cases. CASE PRESENTATION: We report the case of a 33-year-old patient who underwent a kidney transplant in January of 2018. After transplantation, he reached a creatinine value of 1.1 mg/dL and a hemoglobin (Hb) level of 14 g/dL. In April 2019, he developed mycoplasma pneumonia, with signs of hemolytic anemia on bone marrow aspiration. Eventually, he was admitted because of fever, arthralgia, and anemia, with serologic and bone marrow biopsy evidence of red cell aplasia secondary to parvovirus B19 infection. He was treated with 400 mg/kg intravenous immunoglobulin (IVIg) for 10 days; 18 days after the end of treatment, he reached a creatinine value of 1.15 mg/dL, an Hb of 12.5 g/dL, and a reduction of the viral load from 25,000,000 copies/mL to 1,600,000 copies/mL. CONCLUSIONS: Anemia with both an aplasic and hemolytic component was successfully treated using immunoglobulin therapy, with a significant fall in the parvovirus B19 viral load.

Hemophagocytic Lymphohistiocytosis in Renal Transplant Recipients: A 2-Case Report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by an excessive immune activation. HLH can be triggered by a variety of events that disrupt immune homeostasis, such as infections and immunosuppression. HLH presents with heterogeneous clinical symptoms and laboratory findings such as pancytopenia, elevated liver enzymes, impaired renal function, and hyperferritinemia. CASE PRESENTATIONS: Case 1. A 58-year-old man was admitted because of a high fever and diarrhea. Laboratory findings showed acute renal impairment, pancytopenia, Epstein-Barr virus (EBV) DNA seropositivity with a replication index of 2 million copies/mL, and hyperferritinemia. A diagnosis of HLH was confirmed by bone marrow aspiration. He was treated with etoposide, steroids, and rituximab with initial good response and good kidney function restoration. He was discharged after 31 days but eventually died after 44 days after a disease relapse. Case 2. A 51-year-old kidney transplant recipient was admitted because of a fever of unknown origin. A worsening renal function, pancytopenia, EBV DNA of 4,356,222 copies/mL on blood, D-Dimer 7505 ng/mL, ferritinemia 9180.9 ug/L, and triglycerides 1273 mg/dL were found. Bone marrow aspiration was negative for HLH; a few days later, a diagnosis of HLH was made after a positive bone marrow biopsy. Continuous renal replacement therapy was started in the intensive care unit because of severe lactic acidosis due to sepsis. She died few days later. CONCLUSION: EBV infection could be a trigger for HLH in a renal transplant patient. Hyperferritinemia is useful for differential diagnosis in a septic patient. The outcome is very poor even with prompt treatment.

KIR and their HLA Class I ligands: Two more pieces towards completing the puzzle of chronic rejection and graft loss in kidney transplantation.

BACKGROUND: Kidney transplantation is a life-saving treatment for patients with end-stage renal disease. However, despite progress in surgical techniques and patient management, immunological rejection continues to have a negative impact on graft function and overall survival. Incompatibility between donors and recipients for human leukocyte antigens (HLA) of the major histocompatibility complex (MHC) generates a series of complex cellular and humoral immune response mechanisms that are largely responsible for rejection and loss of graft function. Within this context, a growing amount of evidence shows that alloreactive natural killer (NK) cells play a critical role in the immune response mechanisms elicited by the allograft. Killer immunoglobulin-like receptors (KIRs) are prominent mediators of NK cell alloreactivity. METHODS AND FINDINGS: A cohort of 174 first cadaveric kidney allograft recipients and their donors were selected from a total cohort of 657 transplanted patients for retrospective immunogenetic analyses. Patients with HLA Class II mismatches were excluded. HLA Class I allele frequencies were compared among patients with chronic rejection, patients with stable graft function and a group of 2388 healthy controls. Activating and inhibitory KIR gene frequencies, KIR haplotypes, KIR-HLA ligand matches/mismatches and combinations of recipient KIRs and donor HLA Class I ligands were compared among patients with and without chronic rejection and a group of 221 healthy controls. Patients transplanted from donors homozygous for HLA-C1 antigens had a significantly higher risk for chronic rejection than patients transplanted from donors homozygous or heterozygous for HLA-C2 antigens or with epitopes belonging to the HLA-Bw4 ligand group. The Kaplan-Meier curves obtained by dividing the patients into 3 groups according to the presence or absence of one or both of the combinations of recipient KIRs and donor HLA ligands (rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4) showed a significantly higher cumulative incidence of chronic rejection in the group of patients completely lacking these functional units. These patients showed a progressively stronger decline in modification of diet in renal disease-estimated glomerular filtration rate. CONCLUSIONS: KIR genotyping should be performed at the time of enrolment of patients on the waiting list for organ transplantation. In our study, a significantly higher risk of chronic rejection after kidney transplantation was observed when recipient (r) and donor (d) pairs completely lacked the two functional rKIR-dHLA ligand combinations rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4. This immunogenetic profile corresponds to low levels of NK cell inhibition. Therefore, patients with this high risk profile could benefit from immunosuppressive therapy aimed at reducing NK-cell cytotoxicity.

Interleukin 1, interleukin 6, interleukin 10, and tumor necrosis factor α in active and quiescent systemic lupus erythematosus.

OBJECTIVES: Several studies have investigated the cytokine profile of patients with systemic lupus erythematosus (SLE); however, their role is still controversial, mostly because SLE has a heterogeneous disease manifestation. We measured 4 of the most important cytokines in patients with SLE after dividing them in uniform groups according to disease activity and organ involvement. MATERIALS AND METHODS: Eighty-two adult female patients with SLE were divided into 3 groups according to disease activity and organ involvement: Group A (SLE activity index [SLEDAI] score, 7 ± 0.4) included subjects with newly diagnosed, active SLE, investigated before starting therapy. Group B (SLEDAI score, < 6) included patients without renal involvement, treated with prednisone and azathioprine or hydroxychloroquine. Group C (SLEDAI score, < 6) included patients with lupus nephritis, treated with methylprednisolone and cyclophosphamide, reaching complete remission. Fourteen healthy females served as controls. RESULTS: Interleukin-1 levels were 1.0, 0.8, 0.7, and 0.25 pg/mL in groups A, B, C, and D, respectively. Interleukin-6 levels were 3.2, 3.6, 4.0, and 1.4 pg/mL in groups A, B, C, and D, respectively; Il-10 levels, 3.05, 1.1, 1.5, and 1.65; tumor necrosis factor-α levels, 8.75, 5.8, 5.4, and 3.6. Interleukin 1, IL-6, and tumor necrosis factor-α were significantly higher in the patients with SLE than in the healthy controls; IL-1 was significantly higher in group A than in group C. Interleukin 10 showed positive correlation with C-reactive protein, whereas it showed negative correlation with C3. CONCLUSIONS: Data from our cohort, one of the largest so far reported, add to the evidence that proinflammatory cytokines such as Interleukin-1, Interleukin-6, Interleukin-10 and tumor necrosis factor-α are important in SLE pathogenesis.