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Hans H Hirsch

Publications and source records attributed to Hans H Hirsch.

12 recordsLinked to original sources
PubMed2026

Benchmarking urinary cell transcriptomes for noninvasive differentiation of BK polyomavirus-associated nephropathy from T cell-mediated rejection.

BK polyomavirus-associated nephropathy (BKVN) adversely impacts kidney allograft survival and often mimics acute T cell-mediated rejection (TCMR), confounding diagnosis and management. To address this conundrum, we performed unbiased RNA sequencing of urinary cells matched to biopsies classified as BKVN with intragraft inflammation (BKVN-P), BKVN without inflammation (BKVN-N), TCMR, or no rejection (NR). BKVN-N displayed dominant host DNA replication, cell cycle, and repair programs, while BKVN-P samples exhibited expansive innate immune activation, antigen presentation, chemokine upregulation, and epithelial injury. Both BKVN subtypes shared signatures of T cell exhaustion and mature and tolerogenic dendritic cell activation but differed in immune orientation - Th1 predominance in BKVN-N versus Treg and CD8 enrichment in BKVN-P. Compared with TCMR samples, BKVN-P lacked robust TCR/CD28 signaling and was enriched for viral and innate modules; BKVN-N lacked alloimmune activation. B cell exhaustion characterized BKVN-N, while BKVN-P displayed robust B cell activation with metabolic downregulation. A ratiometric urinary cell biomarker, CXCL10 mRNA/CD3E mRNA, distinguished both BKVN subtypes from TCMR with diagnostic accuracy, replicated by quantitative reverse transcription PCR for clinical translation, and confirmed in an independent cohort. These findings demonstrate the utility of urinary cell transcriptomics for resolving viral injury from alloimmunity, enabling precision diagnostics and targeted immunomodulation in kidney transplantation.

Humans↗
PubMed2004

BK virus-associated nephropathy in renal allograft recipients: rescue therapy by sirolimus-based immunosuppression.

BACKGROUND: BK virus nephritis (BKN) in recipients of renal allografts has reemerged during the past 5 years. Despite increased incidence, therapeutic options remain limited and progression of the disease often leads to allograft failure. METHODS: From May 2002 to July 2002, we performed protocol biopsies in 25 recipients of kidney allografts with progressive allograft dysfunction; three patients demonstrated unexpected histopathologic features of BKN. We tested the hypothesis that replacement of their lymphocytotoxic and nephrotoxic immunosuppression (combination of mycophenolate and tacrolimus) with sirolimus- and prednisone-based therapy can lead to disappearance of the virus without increasing the risk of acute rejection. RESULTS: During the median follow-up of 18 months after sirolimus and prednisone therapy, decoy cells disappeared first, followed by progressive decrease in the median plasma BK virus-DNA load, and undetectable levels at the last follow-up. Patients remained free of acute rejection, and follow-up median estimated creatinine clearance increased to 67 mL/min (range 62-75 mL/min) from 52 mL/min (range 51-54 mL/min) at the time of diagnosis. CONCLUSIONS: Further studies are needed, but at present these preliminary results offer a new direction for therapeutic intervention in recipients of renal allografts with BKN.

Adult↗
PubMed2004

Immune reconstitution in HIV-infected patients.

The prognosis of patients infected with human immunodeficiency virus (HIV) type 1 has dramatically improved since the advent of potent antiretroviral therapies (ARTs), which have enabled sustained suppression of HIV replication and recovery of CD4 T cell counts. Knowledge of the function of CD4 T cells in immune reconstitution was derived from large clinical studies demonstrating that primary and secondary prophylaxis against infectious agents, such as Pneumocystis jirovecii (Pneumocystis carinii), Mycobacterium avium complex, cytomegalovirus, and other pathogens, can be discontinued safely once CD4 T cell counts have increased beyond pathogen-specific threshold levels (usually >200 CD4 T cells/mm3) for 3-6 months. The downside of immune reconstitution is an inflammatory syndrome occurring days to months after the start of ART, with outcomes ranging from minimal morbidity to fatal progression. This syndrome can be elicited by infectious and noninfectious antigens. Microbiologically, the possible pathogenic pathways involve recognition of antigens associated with ongoing infection or recognition of persisting antigens associated with past (nonreplicating) infection. Specific antimicrobial therapy, nonsteroidal anti-inflammatory drugs, and/or steroids for managing immune reconstitution syndrome should be considered.

Antiretroviral Therapy, Highly Active↗
PubMed2004

Acute renal failure on immune reconstitution in an HIV-positive patient with miliary tuberculosis.

Immune reconstitution syndrome following HAART in human immunodeficiency virus (HIV)-infected patients is characterized by inflammatory worsening of organ functions despite improvement in HIV surrogate markers of HIV infection. We describe a patient with miliary tuberculosis and urinary shedding of acid fast bacilli who developed acute renal failure 8 weeks after initiation of antituberculosis therapy and 6 weeks after initiation of HAART. The diagnostic workup and further course of disease implicated immune reconstitution syndrome as the cause of acute renal failure.

Acute Kidney Injury↗
PubMed2004

Histological patterns of polyomavirus nephropathy: correlation with graft outcome and viral load.

Polyomavirus-associated nephropathy (PVAN) is a significant cause of allograft loss. The diagnosis requires allograft biopsy, but the impact of the histological features on diagnosis and outcome has not been described. We studied the distribution and extent of PVAN in 90 patients. Viral cytopathic changes, tubular atrophy/fibrosis and inflammation were semi-quantitatively scored and classified into histological patterns. The histological findings were correlated with viruria, viremia and graft survival. PVAN lesions were random, (multi-)focal and affected both cortex and medulla. Areas with PVAN coexisted with areas of unaffected parenchyma. In 36.5% (15/41) of biopsies with multiple tissue cores, discordant findings with PVAN-positive and -negative cores were observed. However, all patients with PVAN had decoy cells in urine as well as significant viruria and viremia (mean of 2.5 x 10(8) and 2.32 x 10(7) viral copies, respectively). Biopsies showing lesser degrees of renal scarring at the time of diagnosis were associated with, more likely, resolution of the infection, in response to decrease of immunosuppression (p = 0.001). More advanced tubulointerstitial atrophy, active inflammation and higher creatinine level at diagnosis correlated with worse graft outcome (p = 0.0002, 0.0001 and 0.0006). Due to the focal nature of PVAN, correlation of biopsy results with viruria and viremia are required for diagnosis.

Biopsy↗
PubMed2004

Epstein-Barr virus load correlating with clinical manifestation and treatment response in a patient with angioimmunoblastic T-cell lymphoma.

Epstein-Barr virus (EBV)-associated lymphoma may arise secondary to angioimmunoblastic T-cell lymphoma (AITL). The prognosis is poor despite chemotherapy and experimental therapies. We report on a 40-year-old woman with AITL without obvious immunodeficiency in which EBV-associated lymphoma developed. The occurrence and size of enlarged lymph nodes correlated strongly with the EBV load in serum (EBVL). Treatment with valacyclovir at the early stage resulted in a drastic more than 3 log10 decrease of EBVL and complete remission. However, valacyclovir had to be stopped after 6 months due to side effects, and the lymphoma reoccurred 3 months later associated with increasing EBVL. Eventually started cytotoxic chemo- and anti-CD20 therapy resulted only in partial remission. The lymphoma progressed and 33 months after it was diagnosed the patient died. This case report demonstrates the close association of EBVL and AITL and a beneficial effect of antiviral therapy at an initial stage of disease manifestation.

Acyclovir↗
PubMed2003

A controlled trial of granulocyte macrophage-colony stimulating factor during interruption of HAART.

OBJECTIVES: To explore the effect of granulocyte macrophage colony stimulating factor (GM-CSF) on viral load and CD4 cell count during interruption of highly active antiretroviral therapy (HAART). METHODS: Patients on effective HAART (CD4 cell count > 400 x 10(6)/l; viral load < 50 HIV RNA copies/ml) were randomized to one of two groups: 12 weeks' treatment interruption plus, during the first 4 weeks, 300 microg GM-CSF (Leucomax-Novartis) by subcutaneous injection three times weekly (GM-CSF group); 12 weeks' scheduled treatment interruption (STI-only group). Viral load, CD4 cell count, clinical events and side effects of treatment were monitored. RESULTS: Thirty-three patients, 15 in the GM-CSF group and 18 in the STI-only group, were evaluated according to the intention-to-treat principle. The two groups were well matched with regard to pre-HAART viral loads and CD4 cell counts. During STI, viraemia was approximately two to three times lower in the group receiving GM-CSF (max 4.97 versus 5.45 in STI-only group; P = 0.03). Fifteen out of 17 patients in the STI-only group showed a decrease in their CD4 cell count between weeks 0 and 4 (median decrease 231 x 10(6) cells/l; P < 0.001); there was no such tendency in the GM-CSF group (P = non-significant when comparing CD4 cell counts at weeks 0 and 4). The median CD4 cell AUC (area under the curve) from week 0 to week 12 was higher in the GM-CSF group (9166 cells.week) than in patients without GM-CSF (7257), P = 0.02. GM-CSF produced local reactions in 88% of patients, and generalized symptoms such as fever, back pain or headache in 82% of patients. Seventy-six percent of patients completed the planned course of 12 injections. CONCLUSIONS: The administration of GM-CSF blunted the viral rebound following interruption of HAART, and largely prevented a decrease of CD4 cell counts during a 12-weeks-treatment interruption. A better understanding of the underlying mechanism(s) may help to identify synergistic treatment targets and improved administration protocols to enhance control of chronic HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Polyomavirus BK.

Polyomavirus hominis 1, better known as BK virus (BKV), infects up to 90% of the general population. However, significant clinical manifestations are rare and limited to individuals with impaired immune functions. BKV has been associated with diverse entities such as haemorrhagic cystitis, ureteric stenosis, vasculopathy, pneumonitis, encephalitis, retinitis, and even multi-organ failure. In addition, BKV has been implicated in autoimmune disease and possibly cancer. Due to high prevalence and frequent reactivation, the role of BKV in some of these pathologies has been difficult to define. Development of BKV diseases is likely to require complementing determinants in the host, the target organ, and possibly the virus, that are subject to modulators such as immunosuppression. These complex aspects are highlighted in polyomavirus-associated nephropathy (PAN), an emerging disease in renal allograft recipients that may jeopardise the progress in renal transplantation accomplished in the past 10 years. Intervention is difficult due to the lack of specific antivirals and relies mostly on improving immune control. Diagnostic strategies using urine cytology and BKV load measurements in plasma have led to earlier diagnosis of PAN, which increased the success rate of intervention. Case series suggest that cidofovir might be effective, especially when combined with reduced immunosuppression.

Antiviral Agents↗
PubMed2002

Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients.

BACKGROUND: Nephropathy associated with the polyomavirus type BK (BKV) nephropathy has emerged as a cause of allograft failure linked to immunosuppressive regimens containing tacrolimus or mycophenolate mofetil. The presence of viral inclusions, known as "decoy cells," in urine and the presence of BKV DNA in plasma have been proposed as markers for the replication of BKV and associated nephropathy, but data from prospective studies have been lacking. METHODS: In a prospective, single-center study, we followed 78 renal-transplant recipients who were receiving immunosuppressive therapy that included tacrolimus (37 patients) or mycophenolate mofetil (41 patients). Urine was tested for the presence of decoy cells at routine visits. BKV DNA was measured 3, 6, and 12 months after transplantation and whenever decoy cells were detected. The viral load in plasma was quantified with the use of a real-time polymerase-chain-reaction method. Renal biopsy was performed if allograft function deteriorated. RESULTS: Twenty-three patients had decoy-cell shedding a median of 16 weeks after transplantation (range, 2 to 69), 10 patients had BKV viremia at a median of 23 weeks (range, 4 to 73), and 5 had BKV nephropathy at a median of 28 weeks (range, 8 to 86). Kaplan-Meier estimates of the probability of decoy-cell shedding, viremia, and nephropathy were 30 percent (95 percent confidence interval, 20 to 40 percent), 13 percent (95 percent confidence interval, 5 to 21 percent), and 8 percent (95 percent confidence interval, 1 to 15 percent), respectively. Antirejection treatment, particularly with corticosteroids, was associated with BKV replication and nephropathy. The viral load in plasma was higher in patients with BKV nephropathy than in those without nephropathy (P<0.001 by the Mann-Whitney test). BKV antibodies were detected in 77 percent of the 78 patients before transplantation, including 4 of 5 with BKV nephropathy. CONCLUSIONS: BKV nephropathy in renal-transplant recipients represents a secondary infection associated with rejection and its treatment in most cases and could be monitored by measuring the viral load in plasma.

Adult↗
PubMed2002

Late Aspergillus fumigatus endomyocarditis with brain abscess as a lethal complication after heart transplantation.

We report the case of a 65-year-old male patient who died from lethal Aspergillus fumigatus endomyocarditis and multiple cerebral septic emboli 6 months after cardiac transplantation. This complication developed 4 weeks after diagnosis of bilateral pulmonary aspergillosis, which was immediately treated by surgical removal and intravenous amphotericin B. Preceding colonization with Aspergillus spp was not identified. Primary cytomegalovirus infection (donor+/recipient-) and toxoplasmosis reactivation (donor+/recipient+) occurring at 1 and 2 months post-transplantation were successfully treated.

Aged↗
PubMed2002

Polyomavirus BK nephropathy: a (re-)emerging complication in renal transplantation.

Persisting polyomavirus replication is now widely recognized as a (re-)emerging cause of renal allograft dysfunction. Up to 5% of renal allograft recipients can be affected about 40weeks (range 6-150) post-transplantation. Progression to irreversible failure of the allograft has been observed in up to 45% of all cases. The BK virus strain is involved in the majority of the cases. Risk factors may include treatment of rejection episodes and increasing viral replication under potent immunosuppressive drugs such as tacrolimus, sirolimus or mycophenolate. The diagnosis requires the histological demonstration of nuclear polyomavirus inclusions in affected tubular epithelial cells. Interstitial inflammatory infiltrates and fibrosis become more prominent in the persisting disease and may be difficult to distinguish from (coexisting) rejection. Detection of polyomavirus-inclusion bearing cells ('decoy cells') in the urine and quantification of BK virus DNA in the plasma have been proposed as surrogate markers for polyomavirus replication and allograft disease, respectively. Antiviral treatment is not yet established; however, reports of treatment with cidofovir are encouraging. Current management aims at the judicious modification and/or reduction of immunosuppression which, in view of preceding or concurrent rejection, is not without risk.

BK Virus↗