Prevalence of IgG subclasses (IgG1/IgG3) in Antenatal Alloimmunized Women: Experience in a Tertiary Hospital in South India

OBJECTIVE: To study the prevalence of IgG subclasses (IgG1 and IgG3) in antenatal alloimmunized women in South India and to correlate it with occurrence and severity of Hemolytic Disease of Fetus and Newborns (HDFN). METHODOLOGY: 85 antenatal women with a positive antibody screen were included in this study, irrespective of parity and period of gestation. The antibodies were identified and IgG subclass (IgG1/ IgG3) was determined using the “DAT IgG1/IgG3 ID card from DiaMed Gmbh, BIO-RAD which utilizes the column agglutination technique. These pregnancies were followed up to see the outcome. The newborn was identified to “have or not have HDFN” using the DAT test and further categorized into Mild/ Moderate/Severe HDFN based on the modality of treatment required. The prevalence of IgG1/IgG3 subclasses was calculated in the alloimmunized antenatal. The categorical data including disease IgG subclass, severity of HDFN and correlation with DAT strength was calculated using Pearson’s chi square test. The severity of HDFN was correlated with the IgG (IgG1 and IgG3) subclasses and antibody titre levels in maternal serum using the univariate and binary logistic regression analysis. RESULTS AND CONCLUSION: The prevalence of IgG subclasses in our study was found to be, 20% for IgG1, 4% for IgG3, 25% for IgG1+ IgG3, 51% had neither IgG1 and/or IgG3. Among the 57 newborns at risk of HDFN, we found a highly significant difference between disease severity and absence / presence of IgG1/IgG3 – either singly or in combination (p<0.001). Assessing disease severity in low and intermediate antibody titre level groups showed a significant difference with more severe disease in those with IgG1 and / or IgG3 as compared to those who were negative for both these subclasses (p<0.001). The binary logistic regression analysis showed the odds of severe HDFN to increase an additional seven times stepwise , the lowest being in patients with neither IgG1/IgG3, to having either one of them, to having both these subclasses together (p<0.05, CI between 1.5-31.89). DAT was positive in 37 of 57 babies. Severity of HDFN was significantly associated with increasing DAT strength (p<0.001). We conclude that the presence of IgG1/IgG3 subclass impacts significantly on the severity of HDFN. This effect continues to be significant even when titres are low. These mothers therefore require closer antenatal monitoring, and babies in this group require closer follow up to allow for appropriate and timely intervention. A stronger DAT reflects as HDFN with greater severity. This study identified the significance of IgG subclass as an independent prognostic marker for HDFN which can easily be incorporated into routine clinical practice

THE SUBTYPES OF PANCREATIC DUCTAL ADENOCARCINOMAS

Being the 4th leading cause of cancer deaths in the U.S. and with a global increase in incidence, above 80% of pancreatic cancers are locally advanced or metastatic at the time of diagnosis. As surgical resection is the only hope for a cure, the answer is probably in early screening, proper classification and right therapy. The advancing research will likely lead to a better understanding of Pancreatic Ductal Adenocarcinoma (PDAC) as well as enhance the techniques for screening, diagnosis, accurate subtyping and enable the use of targeted therapy. Thus, instead of clubbing together various subtypes of PDAC for trials, improving the subcategorization will ensure statistical significance for the academicians, and the clinicians would avoid administration of placebo drug to a vast number of patients

THE SUBTYPES OF PANCREATIC DUCTAL ADENOCARCINOMAS

Being the 4th leading cause of cancer deaths in the U.S. and with a global increase in incidence, above 80% of pancreatic cancers are locally advanced or metastatic at the time of diagnosis. As surgical resection is the only hope for a cure, the answer is probably in early screening, proper classification and right therapy. The advancing research will likely lead to a better understanding of Pancreatic Ductal Adenocarcinoma (PDAC) as well as enhance the techniques for screening, diagnosis, accurate subtyping and enable the use of targeted therapy. Thus, instead of clubbing together various subtypes of PDAC for trials, improving the subcategorization will ensure statistical significance for the academicians, and the clinicians would avoid administration of placebo drug to a vast number of patients

A Rare CD4−CD8+ Adult T-Cell Leukemia/Lymphoma with Unique Molecular Mutations: A Case Report with Literature Review

Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell neoplasm caused by infection of the human T-cell lymphotropic virus type 1 (HTLV-1). Most ATLL cases are CD4-positive and CD8-negative. Though rare, there are a few dual negative (CD4−CD8−), dual positive (CD4+CD8+), and CD4−CD8+ cases reported in literature. ATLL is associated with HTLV-1 infection, but HTLV-1 alone cannot cause the malignant transformation of infected T cells. Additional genetic and/or epigenetic events are required for the development of the disease. Here, we report an unusual CD4−CD8+ATLL in a 76-year-old male with a unique molecular genetic profile. Molecular studies revealed alterations in 10 genes. Three of them are predicted to be pathogenic by the computational models, including the frameshift change in ZFHX4 and missense mutations in RHOA and POT1. The specific mutations of POT1 (c.281A > G; p.Q94R), RHOA (c.47G > A; p.C16Y), and ZFHX4 (c.2871delC; p.F958Sfs∗31) have never been previously reported in ATLL to the best of our knowledge. The clinical significance of other genetic alterations is unknown. Further research is warranted to correlate this patient’s molecular findings with other ATLL cases. Correlation specifically with other cases of CD8+ ATLL could prove to be useful in understanding the pathogenesis of this rare variant of an already rare form of leukemia/lymphoma

Clinical significance of pathologic abnormalities in biopsy samples from the appendiceal orifice

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/170899/1/his14418_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/170899/2/his14418.pd