Maria Campione

Intrahepatic IgG/IgM plasma cells ratio helps in classifying autoimmune liver diseases

BACKGROUND/AIM Plasma cells infiltrate in the liver is a prototype lesion of autoimmune liver diseases. The possible role of plasma cells isotyping (IgM and IgG) in the liver in the diagnostic definition of autoimmune liver disease, and particularly in variant syndromes such as autoimmune cholangitis and the primary biliary cirrhosis/autoimmune hepatitis overlap syndrome, is less defined. METHODS We analysed the clinical, serological and histological features of 83 patients with autoimmune liver disease (40 primary biliary cirrhosis, 20 autoimmune hepatitis, 13 primary sclerosing cholangitis, 4 autoimmune cholangitis and 6 overlap syndrome) compared to 34 patients with chronic hepatitis C and evaluated the expression of IgM and IgG plasma cells in their liver by immunostaining. RESULTS By Spearmans correlation, the mean-counts of IgM plasma cells in portal tracts were significantly correlated with female gender, serum alkaline phosphatase, gamma-glutamyl transferase and IgM values, positivity for anti-mitochondrial antibody-M2 and, on liver biopsy, with bile duct changes, orcein-positive granules and granulomas. Whereas IgG plasma cells resulted more correlated with alanine aminotransferase levels. IgG/IgM ratio lower than 1 was found no only in primary biliary cirrhosis but also in all patients with autoimmune cholangitis. Conversely, all patients with overlap syndrome showed IgG/IgM ratio higher than 1. CONCLUSION Immunostaining for IgM and IgG plasma cells on liver tissue can be a valuable parameter for better diagnosis of autoimmune liver disease and also for variant or mixed syndromes.

Predictive role of histological features and Ki67 pattern on high-risk HPV presence in atypical cervical lesions.

the Laboratory of HealthCare Associated Infection, Specialist and Reference Microbiology Division, Colindale, UK, demonstrated S. aureus positive for the PVL gene. Molecular studies by polymerase chain reaction on the postmortem tissue were negative for all influenza, Para influenza, respiratory syncytial and adeno-viruses. Antemortem serological tests for Legionella, mycoplasma, Q fever and psittacosis were also negative. It was concluded that this was haemorrhagic necrotizing pneumonia occurring in a young immunocompetent patient due to S. aureus strain carrying the PVL gene. This was regarded as ‘community acquired’ in our case, as the patient already had established features of pneumonia and septicaemia on admission. Epidemiological evidence so far also suggests that this PVL strain of MRSA is community acquired in most circumstances. As the patient was not immunocompromised, her neutropenia appeared to be the effect of the leukocytotoxic PVL toxin as well as secondary to septicaemia and DIC. Staphylococcus aureus is responsible for about 2% of cases of community-acquired pneumonia and at least 10% of cases of nosocomial pneumonia. Staphylococcus aureus carrying the PVL gene strain is responsible for the community-acquired pneumonias. CA-MRSA has several distinguishing features from hospital acquired (HA)-MRSA, including: presence of the SCCmec IV element and the presence of a gene encoding the PVL toxin; they are more virulent, although relatively sensitive to antibiotics. Depending on multi-locus sequence typing and pulsed-field gel electrophoresis, Vandenesch et al. and Charlebois et al. have concluded that the genetic substance of CA-MRSA and HA-MRSA is diverse and distinct, indicating that CA-MRSA are true strains originating from the community. Therefore, PVL-MRSA ⁄ CAMRSA seems to be a specific disease entity with a poor prognosis. This poor prognosis is probably related to the PVL toxin, which is an extracellular product with a leucocytotoxic action. The prevalence of CA-MRSA is not known, but it can be distinguished from the nosocomial strains clinically by its susceptibility profile (Ciprofloxacin susceptible, fusidic acid resistant). The pathological findings in this case are similar to the (limited) pathology findings described in the literature. The gross appearance of the lungs is similar to either viral pneumonia or adult respiratory distress syndrome, and is different from suppurative pneumonia due to other bacterial infections. Histological features are also distinctly different from other forms of staphylococcal pneumonia with no evidence of suppuration. They more resemble viral pneumonia, except, of course, for the lack of viral inclusions and the presence of large colonies of Gram-positive cocci. Although PVL gene-carrying MRSA pneumonia ⁄ CA-MRSA pneumonia has been reported and recognized in the literature, it is not widely recognized by histopathologists and the detailed pathology of lungs has not been well described. This has important implications. CA-MRSA is likely to present as an acute fulminating illness in previously healthy immunocompetent young adults, culminating in death (within a short period of time). As histopathologists are likely to be performing autopsies in such cases, lack of knowledge of the existence (and pathology) of CA-MRSA ⁄ PVL-MRSA could result in an erroneous diagnosis and cause of death.