CD44 immunoreactivity in the developing human kidney: a marker of renal progenitor stem cells?

CD44 is a transmembrane adhesion glycoprotein, functioning as a hyaluronan receptor and participating in the uptake and degradation of hyaluronan. Recently, CD44 has been proposed in the adult kidney as a marker of activated glomerular parietal epithelial cells, the putative niche stem cells that, in case of damage to podocytes, might migrate inside the glomerular tuft and undergo transition to podocytes. Here, immunoreactivity for CD44 was tested in 18 human fetuses and newborns with a gestational age ranging from 11 to 39 weeks. CD44 immunoreactivity was observed in all but one developing kidneys, being localized in several renal cell types including intraglomerular, capsular, cortical and medullary interstitial cells and nerve cells. In some cases, CD44 marked scattered cells in nephrogenic subcapsular zone. Our data indicate that CD44 is involved in human nephrogenesis, probably marking a subset of progenitor/stem cells involved in early phases of kidney development and, putatively, in podocyte and/or interstitial cell differentiation.

[The origins of the Renal Immunopathology Group of the Italian Society of Nephrology].

This article describes the birth and development of the Renal Immunopathology Group of the Italian Society of Nephrology. It collects the stories of nephrologists and pathologists who, since the early Seventies up to the first decade of this century, devoted their professional lives to the study of renal pathology with a strong personal involvement, characterized by enthusiasm, commitment, ability, strong spirit of cooperation, and friendship. All this enabled the Group to: propose the criteria for a standardized histological and immuno-histological examination of renal biopsies and reporting; produce several multicenter studies, whose results were also published in important international journals; to set up a national registry of renal biopsies; to organize a number of courses, some of which were associated with the publication of monographs, on various renal diseases. This article also traces the history of renal pathology in Italy from the second half of the Sixties - when young Italian nephrologists and pathologists from different institutions moved to French laboratories to learn new techniques to apply to renal biopsies - up to the present days. It also shows us how Italian renal pathology has been an essential tool for the development of the nephrological clinical practice and the advancement of scientific research.

Serological evidence of vertical transmission of JC and BK polyomaviruses in humans.

Vertical transmission of JC virus and BK virus has been investigated by few authors, with conflicting results. We performed a combined serological and genomic study of 19 unselected pregnant women and their newborns. Blood and urine samples were collected during each gestational trimester from the pregnant women. Umbilical cord blood, peripheral blood, urine and nasopharyngeal secretion samples were taken from newborns at delivery and after 1 week and 1 month of life. Polyomavirus DNA was detected by nested PCR. Polyomavirus IgG-, IgM- and IgA-specific antibodies were measured in maternal and newborn serum samples using a virus-like-particle-based ELISA method. BKV and JCV DNA were detected in urine from 4 (21 %) and 5 (26 %) women, respectively. BKV and JCV seroprevalences in the pregnant women were 84 % and 42 %, respectively. Using a rise in the IgG level or the transient appearance of an IgA or IgM response as evidence of infection in the newborn, we detected BKV and JCV infections in four (21 %) and three (16 %) newborns, respectively. Three infants had serological evidence of infection with both BKV and JCV. In two of the four possible BKV-infected newborns, the mothers seroconverted during pregnancy, while another mother was viruric and IgA seropositive. The mother of one of the three possible JCV-infected newborns was viruric and IgA seropositive; another mother was viruric. These results suggest JC virus and BK virus can be transmitted from mother to newborn during pregnancy or soon after birth.

Kidney involvement in a patient affected by placental site trophoblastic tumor.

We report a 42-year-old woman who presents a few days after a spontaneous incomplete abortion at the ninth week of pregnancy with hypertension and nephrotic syndrome. Curettage findings and increased values for the ß subunit of human chorionic gonadotrophin were suspicious for a trophoblastic disease. A uterine placental site trophoblastic tumor was diagnosed 2 months later after hysterectomy and treated successfully using chemotherapy. Kidney biopsy showed features consistent with an unusual form of thrombotic microangiopathy characterized by the presence of large thrombus-like structures occluding the capillary lumina and smaller aggregates in the mesangium and along glomerular basement membranes. These deposits were positive for immunoglobulin M, C4, C1q, κ and λ light chains, and fibrinogen. Electron microscopy showed fibrin deposits located primarily in the subendothelial space. The differential diagnosis of this presentation included pre-eclamptic nephropathy, Waldenström disease, lupus anticoagulant glomerulonephritis, systemic lupus erythematosus, and cryoglobulinemic glomerulonephritis. We review the pathogenic mechanisms involved in this case.

BK virus sequences in specimens from aborted fetuses.

Given the conflicting results of the few published studies, the aim of this retrospective molecular-based study of 10 aborted fetuses that underwent complete autopsy and 10 placentas was carried out to determine whether BK polyomavirus (BKV) can be transmitted transplacentally. The interruption of pregnancy was due to a miscarriage (five cases) or a prenatal diagnosis of severe intrauterine malformations (five cases). Samples from the brain, heart, lung, thymus, liver, and kidney were taken from each fetus, and two samples were obtained from all of the placentas. The presence of BKV was investigated by means of PCR using primers specific for the transcription control region (TCR) and viral capsidic protein 1 (VP1) and DNA extracted from formalin-fixed, paraffin-embedded tissue. BKV genome was detected in 22 of 60 samples (36.6%) from seven fetuses (70%), regardless of the cause of abortion: VP1 was amplified in 12 samples (54%), TCR in seven (32%), and both in three (14%). VP1 was also detected in one placental sample. BKV sequences were most frequently detected in heart and lung (five cases), but sequence analyses of TCR and VP1 revealed a high degree of genomic variability among the samples taken from different organs and the placenta. These results indicate that BKV can cross the placenta during pregnancy and become latent in fetal organs other than the kidney and brain (previously considered the main targets of BKV latency). This may happen in early pregnancy and does not seem to be associated with an increased risk of abortion.

The reliability of pre-transplant donor renal biopsies (PTDB) in predicting the kidney state. A comparative single-centre study on 154 untransplanted kidneys.

BACKGROUND: Pre-transplant donor biopsy (PTDB) is a common practice in marginal donors, taking for granted that it represents the whole kidney state, but its reliability has not yet been thoroughly investigated. This prompted us to carry out a comparative study on a needle biopsy group (NBG) and a wedge biopsy group (WBG) and their corresponding untransplanted kidneys. METHODS: One hundred and fifty-four biopsies and matched kidneys were scored for four morphologic indexes, i.e. tubular atrophy, interstitial fibrosis, vascular damage and global glomerulosclerosis. Categorical indexes were statistically evaluated for concordance with the k index, and the percentage of sclerotic glomeruli with correlation and linear regression analysis. RESULTS: Agreement between biopsies and kidneys was similar in both NBG and WBG with high scores for vascular damage (k 0.74 and 0.75) and intermediate ones for tubular atrophy (k 0.54 and 0.50). Agreement as to fibrosis and glomerular sclerosis was intermediate in the WBG (k 0.56 and 0.55) and poor in the NBG (k 0. 34 and 0.18). Vascular damage was underscored and glomerulosclerosis overscored in both groups, whereas interstitial fibrosis was underscored in the NBG and overscored in WBG. The agreement for the total score, i.e. the sum of the single indexes, was high in the NBG (k 0.73) and intermediate in WBG (k 0.57). Agreement for glomerulosclerosis and total score rose consistently in both groups along with the increasing number of biopsy glomeruli. There was an agreement as to biopsy and kidney evaluation for fitness for transplantation in 85% of NBG and 81% of WBG. CONCLUSIONS: PTDB supplies reliable data on the actual kidney state, with better results for needle biopsy. Although the biopsy size plays a role, samples with over 10 glomeruli suffice for clinical purposes. Vascular damage is the most faithful single parameter, whereas global glomerulosclerosis estimation requires some caution.

Genomic mutations of viral protein 1 and BK virus nephropathy in kidney transplant recipients.

Genomic variability in the viral protein 1 region of BK polyomavirus (BKV) may change the ability of the virus to replicate. The significance of such changes was studied in clinical samples taken from kidney transplant patients with and without BKV nephropathy. A 94 base-pair fragment of viral protein 1 was amplified from 68 urine, 28 blood, and 12 renal biopsy samples from eight patients with BKV nephropathy, and from 100 urine samples, 17 blood and three renal biopsy samples from 41 of 218 controls. The DNA was sequenced and the amino acid changes were predicted by the Expert Protein Analysis System program (ExPASy, Swiss Institute of Bioinformatics, Geneva, Switzerland). Single base-pair mutations were detected more frequently in the samples from the BKV nephropathy patients than in the controls, and this was the only statistically significant finding of the study (P < 0.05), thus suggesting a greater genetic instability in BKV nephropathy associated strains. The amino acid changes were distributed at random in both BKV nephropathy patients and controls. However, one aspartic acid-to-asparagine substitution at residue 75 was detected in all samples of the one patient with BKV-associated nephropathy, who developed disease progression confirmed by histology, and not in any of the other patient or control samples. Whether this specific amino acid change plays a role in disease deserves further study.

Primary choroid plexus papilloma of the sacral nerve roots.

The authors describe a unique case of a choroid plexus papilloma of the sacral nerve roots. This 60-year-old woman was admitted to the hospital because of a 1-year history of sacral pain, rectal and urinary bladder retention, and paradoxical episodic incontinence. Physical examination revealed sensory abnormalities in the S-2 dermatomes and poor rectal and bladder sphincter contractions. Contrast-enhanced spinal MR imaging showed a well-circumscribed, ovoid, homogeneously enhancing mass at the S1-2 level suggesting a diagnosis of ependymoma or schwannoma, and surgery allowed the identification and complete removal of a soft gray mass intimately adhering to the sacral nerve roots. Histological examination revealed a tumor consisting of papillary structures lined by a single layer of columnar cells, with an immunophenotype that satisfied the diagnostic criteria of choroid plexus papilloma. After diagnosis, contrast-enhanced brain MR imaging excluded the presence of a primary choroid plexus papilloma in the cerebral ventricles, thus ruling out a drop metastasis along the CSF pathways. A review of the literature did not reveal any similar cases of choroid plexus papilloma, and so the authors also discuss the inclusion of primary or metastatic papillary tumors in this unusual location as part of the differential diagnosis.

Pregnancy-related decidualization of subcutaneous endometriosis occurring in a post-caesarean section scar: Case study and review of the literature.

Endometriosis of surgical scars is a rare complication of caesarean sections (incidence: 0.03-0.4%) and other surgical procedures. As endometriosis could be responsive to hormonal stimulation, decidualization and other secondary changes may occur during pregnancy or progestin therapy, sometimes causing a clinically-evident increase in the size of the endometriotic nodules, which could be mistaken for malignant tumors. To our knowledge, we report the 8th subcutaneous case of a pregnancy-related decidualization occurring in a post-caesarean section scar endometriosis. A 33-year-old woman showed a painless, firm, subcutaneous nodule (size: 1 cm) located near the scar of a caesarean section performed 3 years before. Ultrasound examination revealed a well-delimited, hypoechogenic nodule showing perilesional inflammatory reaction without vascular signals. The nodule was considered a post-surgical granuloma: its size did not increase during 4 years of follow-up. Finally, the nodule was totally excised during a second caesarean section performed at 39 weeks of gestation. Histological examination showed nodules of decidualized stromal cells surrounding rare, small, atrophic endometrial glands. Nuclear atypia and mitoses were absent. On immunohistochemical examination, the epithelial cells were pan-CK(AE1/AE3)+/ER+/PR+/S100-/Calretinin-/Vimentin-, while the stromal cells were pan-CK(AE1/AE3)-/Vimentin+/ER+/PR+/CD10+/S100-/Calretinin-. We reviewed the literature, discussing the main clinic-pathological diagnostic pitfalls and the possible differential diagnoses.

Biological and clinical risk factors of chronic lymphocytic leukaemia transformation to Richter syndrome.

Predictors of chronic lymphocytic leukaemia (CLL) transformation to Richter syndrome (RS) are not established and were investigated in 185 consecutive CLL cases. Actuarial incidence of RS (n = 17; all diffuse large B-cell lymphomas) at 10 years was 16.2% (95% confidence interval: 8.0-24.4%). At CLL diagnosis, prognosticators of RS by univariate analysis were IGHV homology >/=98% (P = 0.006), IGHV4-39 usage (P < 0.001), del13q14 absence (P = 0.004), expression of CD38 (P < 0.001) and ZAP70 (P = 0.004), size (P < 0.001) and number (P < 0.001) of lymph nodes, advanced Binet stage (P = 0.002), and lactate dehydrogenase (P < 0.001). Multivariate analysis, performed separately for biological and clinical variables, identified CD38 expression [Hazard ratio (HR) = 4.26; P = 0.018], IGHV4-39 usage (HR = 4.29; P = 0.018), and lymph node size >/=3 cm (HR = 9.07; P < 0.001) as independent RS prognosticators. A multivariate model simultaneously analysing biological and clinical variables identified lymph node size >/=3 cm (HR = 6.51; P = 0.001) and del13q14 absence (HR = 4.08; P = 0.031) as independent RS prognosticators. Risk factors of CLL transformation differed from risk factors of CLL progression. These results suggest that CD38 and del13q14 may identify biological subsets of CLL with different RS predisposition. Predominant nodal disease, CD38 expression, IGHV4-39 usage, and absence of del13q14 may help in predicting RS at CLL diagnosis. Close monitoring and a careful biopsy policy are needed in patients carrying transformation risk factors.

Latent human polyomavirus infection in pregnancy: investigation of possible transplacental transmission.

AIMS: The purpose of the study was to investigate the transplacental transmission of the human polyomaviruses JCV and BKV. METHODS: Urine and blood samples from 300 pregnant women underwent cytological analysis to search for 'decoy cells', nested PCR to identify presence and genotype of isolated polyomaviruses, and sequence analysis of the transcription control region. Nested PCR was also used to study the umbilical cord blood of all their newborns. RESULTS: Decoy cells were identified in only one urine sample (1/300; 0.33%); polyomavirus DNA was detected in 80 urine samples (26.6%) corresponding to BKV alone in 28 samples (9.3%), JCV alone in 49 samples (16.3%) and both JCV-BKV in three samples (1%). Blood samples were positive in 17 cases (5.6%), corresponding to BKV alone in 10 (3.3%), and JCV alone in 7 (2.3%). Rearrangements of the transcription control region were found in only one urinary JCV strain, consisting of the insertion of 13 bp at D block, whereas point mutations were identified in 11 BKV and 11 JCV strains detected from urine. Sequence analysis of the BKV strains detected in blood samples revealed a 20 bp insertion of P block (P42-61) in human chromosomes 20 (five cases) and 14 (three cases); two JCV strains had single bp point mutations. The search for polyomavirus DNA in umbilical cord blood samples was always negative. CONCLUSIONS: Polyomavirus DNA was frequently detected in pregnancy, whereas genomic rearrangements were rare, and no evidence of transplacental transmission of polyomavirus was obtained.

Ciprofloxacin crystal nephropathy.

Ciprofloxacin is a widely used fluoroquinolone for the treatment of patients with complicated and uncomplicated infections. With rare exceptions, only immune-mediated interstitial nephritis was described, with direct renal damage reported only in case of overdose. Experimental studies indicated that crystalluria may be associated with the administration of this drug, but the likelihood that ciprofloxacin crystal nephropathy would occur in humans was believed to be very low on the basis of previous data showing that ciprofloxacin crystalluria depended on a urine pH greater than 6.8. However, we report 2 cases of ciprofloxacin crystal-induced nephropathy with a clinical pattern of acute reversible tubular damage and intratubular crystals identical to that previously described in elderly patients treated with ciprofloxacin dosages within therapeutic schedules. Crystals in the tubules were negative for both the von Kossa stain for phosphates and alizarin red stain for calcium.

Are sequence variations in the BK virus control region essential for the development of polyomavirus nephropathy?

BK virus replication is regulated by the noncoding control region (NCCR); major NCCR rearrangements could modify the strength of viral replication, having a role in the development of polyomavirus-associated nephropathy (PAN). Urine (n = 34), blood (n = 32), and renal biopsy samples (n = 13) from 5 transplant recipients with PAN underwent nested polymerase chain reaction to search for the NCCR region. Sequence analysis was performed on all NCCR fragments obtained. Decoy cells were evaluated semiquantitatively in urine and PAN staged in renal biopsy specimens; the results were related to the presence and type of NCCR sequence variations. Major NCCR rearrangements were found in urine (9/75 [12%]), blood (7/30 [23%]), and renal biopsy (4/15 [27%]) samples in 3 cases; 2 cases had only unrearranged strains. Neither the detection and number of decoy cells nor the PAN stage were related to the specific type of NCCR sequence rearrangements. NCCR rearrangements do not seem essential for the development of PAN.

The prognostic value of renal biopsy in type 2 diabetes mellitus patients affected by diabetic glomerulosclerosis.

BACKGROUND: Although several studies have dealt with clinicopathological correlations in diabetic glomerulosclerosis (DGS), few have investigated the prognostic value of the renal biopsy. METHODS: One hundred and thirty-five type2 diabetes mellitus (DM) patients with bioptically proven DGS and a mean follow-up of 56.1 months were subdivided in 5 groups according to the outcome: 1) living with preserved renal function; 2) living with renal failure, not requiring dialysis; 3) living in dialysis; 4) dead in dialysis; 5) dead with preserved renal function. Duration of DM, creatininemia and proteinuria values at the time of biopsy and a histologic scoring (from 0 to 3) of 10 morphologic features were considered for statistical analysis. RESULTS: Statistically significant differences were observed in the distribution of the above mentioned parameters in the 5 groups with the exception of the duration of DM. The prognosis of DGS is poor: 79 patients needed dialysis and 60 died. Univariate analysis demonstrated the prognostic value of creatininemia (>or= 1.5 mg/dL), proteinuria (>or= 3 g/d) and histologic score (>or= 10) in assessing the relative risk of progression to dialysis (OR= 9.75, 4.12 and 11 respectively). The prognostic value of the histologic score (or= 2) was maintained when each morphologic parameter was separately evaluated (OR ranging from 2.8 to 8.5). Multivariate analysis was applied and only serum creatinine and histological score maintained their statistical significance (OR=4.45 and 2.46). The independence of these two variables means that the risk of progression to dialysis is multiplied in each single patient. CONCLUSIONS: Renal biopsy adds reliable information to that supplied by clinical and laboratory findings in DGS and therefore its extensive adoption should be recommended. Thanks to the prognostic value of the single morphologic parameters, also small tissue samples can give reliable results.

Fine needle aspiration cytology in the diagnosis of non-Hodgkin's lymphomas of the muscle: a report of 2 cases.

BACKGROUND: Primary skeletal muscle lymphoma has been reported in very few cases. Although such imaging techniques as computed tomography and magnetic resonance imaging can supply diagnostic indications, the most reliable data are obtained by means of muscle biopsy investigations. Fine needle aspiration cytology (FNAC) has not been considered before for the diagnosis of muscle lymphoma. CASES: In case 1, 60-year-old man presented with 2 masses in the pectoral muscle and neck. FNAC of the neck mass was performed. The diagnosis was non-Hodgkin's diffuse B-cell lymphoma of the muscle; the diagnosis was confirmed by surgical biopsy of the pectoral muscle. In case 2, a 70-year-old man presented with a mass in the quadriceps muscle. The results of FNAC aroused suspicion of lymphoma, and a muscle biopsy confirmed the presence of a non-Hodgkin's B-cell lymphoma. Immunohistochemistry identified it as non-Hodgkin's marginal zone B-cell lymphoma of MALT type. CONCLUSION: FNAC can be a valuable starting point in muscle involvement by lymphoma because of the possibility of obtaining material by means of multiple aspirations without causing patients any discomfort.

Periodic assessment of urine and serum by cytology and molecular biology as a diagnostic tool for BK virus nephropathy in renal transplant patients.

OBJECTIVE: To investigate the significance of polyomavirus (PV) viruria and viremia by morphologic, immunohistochemical and molecular analysis (multiplex nested-polymerase chain reaction) in renal transplant patients. STUDY DESIGN: Urine (n=328), serum (n= 53) and renal biopsies (n=24) from renal transplant patients (n=106) were studied. RESULTS: Decoy cells were found in 53 samples (16%) from 19 patients (18%); viral DNA was amplified in all urinary samples and disclosed BK virus (BKV) (n=24), JC virus (JCV) (n=16), and JCV and BKV DNA (n=13). BKV was the prevailing genotype in patients with a high frequency of decoy cell excretion (p = 0.001). JCV excretion correlated with a low number (p = 0.01) and BKV with a high number of decoy cells (p=0.003). PV DNA was amplified from 30/53 serum samples (56.6%); BKV was the prevailing genotype (p = 0.04). On 24 renal biopsies (18 from the decoy cell-negative and 6 from the decoy cell-positive group) PV nephropathy (PVN) was identified and BKV DNA amplified in 4 biopsies, all from the group with a high frequency of decoy cell excretion. PVN was not identified in renal biopsies from the decoy cell-negative group. CONCLUSION: PV infection is frequent in renal transplant patients. The BKV genotype in urine and serum is significantly related to a high frequency and high number of decoy cells. PVN occurs only in patients with BKV viremia and a high number and frequency of decoy cell excretion in urine. In the absence of decoy cells, PVN can be excluded. Cytologic analysis of urine is an important diagnostic tool for screening renal transplant patients at risk of PVN.

Different patterns of renal damage in type 2 diabetes mellitus: a multicentric study on 393 biopsies.

The frequency of various types of renal changes in patients with type 2 diabetes is not clearly defined in the literature. Reported discrepancies likely are caused by ethnic and geographic factors. However, policies used in nephrological centers for the selection of patients to undergo renal biopsy also may have an influence. The present study reports 393 renal biopsies in patients with type 2 diabetes performed in a group of centers in northwestern Italy using different (restricted [CRPs] or unrestricted [CUP]) biopsy policies. On the basis of light microscopic, immunofluorescence, and ultrastructural findings, cases were subdivided into three classes characterized by the presence of diabetic glomerulosclerosis (class 1), prevailing vascular (arterioarteriolosclerotic) and ischemic glomerular changes (class 2), other glomerulonephritides superimposed on diabetic glomerulosclerosis (class 3a), or glomerulonephritides without the presence of diabetic glomerulosclerosis (class 3b). Although no significant differences were found for class 2 (detected in 15% and 16% of patients from CRPs and the CUP, respectively), the frequency of the other two classes was strongly biased by the biopsy policy. Class 1 was found in 29% and 51% of cases, and class 3 in 57% and 33% of cases from CRPs and the CUP, respectively. Moreover, class 3a was more common (67%) in the CUP, and class 3b (78%) in CRPs. Our findings may explain conflicting data from the literature and the influence that type of adopted biopsy policy may have on an epidemiological evaluation. This study helps clarify the frequency of renal changes in patients with type 2 diabetes and suggests more extensive use of renal biopsy to obtain reliable prognostic indications and plan a rational therapeutic approach.

Molecular characterisation of JC virus strains detected in human brain tumours.

AIMS: The aim of this study was to evaluate the presence and significance of JC virus (JCV) in human brain tumours. METHODS: Histology, immunohistochemistry (IHC) and molecular biology techniques were employed to examine specimens of tumour tissue, peripheral blood and cerebrospinal fluid taken from 22 patients with primary neuro-epithelial tumours. Furthermore, the coding viral protein (VP1) region and non-coding transcription control region (TCR) of JCV genome isolated from the tumours were submitted to sequence analysis in order to detect viral rearrangements or mutations. RESULTS: JCV genome was found in nine of the 22 tumour specimens (40.9%), including eight astrocyte-derived tumours (seven glioblastomas and one astrocytoma) and one oligodendroglioma, and in two of the 15 cerebrospinal fluid specimens (13.3%) with positive tumour tissue (one glioblastoma and one astrocytoma). Sequence analysis of JCV VP1, which was amplified in seven tissue samples and the two cerebrospinal fluid samples, revealed only genotype 1 (four 1a and three 1b), whereas TCR was amplified in six tissue samples and only one cerebrospinal fluid sample. TCR sequence analysis was possible in four cases and identified three Mad-4 and one type II sequences; the TCR genomic structures of JCV isolated from cerebrospinal fluid were the same as those sequenced from corresponding tumour tissue, thus indicating a possible cerebrospinal fluid dissemination of neoplastic cells carrying viral DNA. CONCLUSIONS: Our results suggest a possible role of JCV in the induction of brain tumours, especially in those originating from brain cells normally targeted by JCV infection.

Renal biopsy interpretation in Alport Syndrome.

Alport Syndrome is a heritable progressive renal disease that, despite the large number of published studies, because of its genetic, clinical, immunohistochemical, and ultrastructural heterogeneity, still remains a diagnostic challenge. The focus of the discussion is on electron microscopy and immunohistochemistry Col (IV) chains. The differential diagnosis from thin glomerular basement membrane disease is discussed in depth, because both are familial, and can have similar clinical presentation and even ultrastructural pathology, but with a different outcome. The diagnostic role of molecular genetics, which identified the presence of collagen IV gene mutations and its relationship to the phenotypic expression of the renal damage, is also discussed.

Sequence analysis of the JC virus transcriptional control region detected in urine from HIV-positive patients.

OBJECTIVE: To investigate the correlation between transcriptional control region (TCR) types and virus replication and the role of decreased host immunity in inducing TCR changes. STUDY DESIGN: In a previous study, urine specimens from 78 unselected HIV-positive patients were independently evaluated by cytology, immunohistochemistry and nested polymerase chain reaction (n-PCR) to detect the presence of polyomaviruses. The JC virus (JCV) large T region was positive in 44/78 (56%) urine specimens by n-PCR. In the current study, these cases further underwent to n-PCR to detect TCR, and the amplified products were sequenced. The JCV types identified were compared using: (1) morphologic evidence of replication (decoy cells and/or immunohistochemical staining of cells detected using anti-SV 40 antiserum), and (2) patients' immune status (CD4+ cell counts). RESULTS: TCR was successfully amplified in 30/44 cases (68%). TCR sequence analysis disclosed 6/30 archetype (20%) and 24/30 archetypelike sequences, the latter distributed as follows: 4 G2 (4/30, 13%) with G-->A substitutions in the C sequence (nt 9), and 20 CY (20/30, 67%) with A-->G substitutions in the F sequence (nt 19). There were no correlations with morphologic evidence of viral replication or immune status. CONCLUSION: The present study indicated that TCR in urine samples from PML-free HIV-positive subjects are archetypes or archetypelike. Immune suppression does not seem to influence minor changes in the TCR genome, and single by mutations do not change JCV replication activity.