Liver Transplant vs Liver Resection in patients with Multifocal hepatocellular Carcinoma.

BACKGROUND: The optimal surgical option in patients with Multifocal hepatocellular Carcinoma (MHCC) is an area of active research. The preference varies based on geographic variations and institutional policies. We sought to determine long-term outcomes in patients with MHCC based on surgical treatment - Liver transplant (LT) vs resection (LR). METHODS: We performed a retrospective analysis of NCDB (2004-2015) and identified patients with MHCC within Milan criteria. Patients with αfetoprotein ≥1000 nanograms/milliliter and those who underwent ablation were excluded. The primary outcome measure was long-term survival in patients undergoing LT vs. LR. The secondary aim of our study was to determine clinicodemographic factors associated with the receipt of LT and LR. RESULTS: 1,546 patients were included, of whom 1,211 received LT and 335 underwent LR. Patients who were non-Hispanic White (70.8% vs.54.9% p <0.01), privately insured (53.7% vs. 36.7%, p <0.01), and treated at academic centers (85.4% vs. 71.6%, p<0.01) were more likely to receive an LT. Multivariable Cox analysis revealed LT was associated with improved survival compared to LR ( HR= 0.34, 95% CI= 0.28-0.42). CONCLUSION: We described clinical and sociodemographic differences in LT and LR patients and found LT to be associated with a decreased mortality risk compared to LR. The study's findings should be interpreted in the context of several limitations, including the selection of MHCC criteria within Milan criteria.

Liver resection is superior to tumor ablation in patients with multifocal hepatocellular carcinoma.

INTRODUCTION: The management of T2 multifocal hepatocellular carcinoma (MHCC) is controversial, and the comparative impact of liver resection (LR) versus tumor ablation (TA) on survival continues to be debated. The aim of our study was to examine short- and long-term survival for LR and TA in a nationally representative cohort. We hypothesized that patients who underwent LR would have improved survival. METHODS: We utilized the National Cancer Database (2004-2015) to identify patients diagnosed with non-metastatic T2 MHCC. Kaplan-Meier survival curves were generated to compare 10-year overall survival (OS) between LR and TA patients. Kaplan-Meier analysis with stratification was also performed based on lymphovascular invasion, resection margin status, and Charlson-Deyo score. Cox proportional hazard models were used in multivariable analyses. RESULTS: A total of 1225 patients met the inclusion criteria. 991 patients received LR, and 234 received TA. The majority of patients were male, White, and older than ≥60 years old. Clinicodemographic characteristics were generally similar between LR and TA patients. Among patients who underwent LR, 84% had negative margins, and 17% had lymphovascular invasion. Mortality at 30 days was significantly higher among LR patients compared to TA patients (5.4% vs 0.0%, p < 0.001), with those having a Charlson-Deyo score ≥2 facing the highest risk at 7.3%. Nevertheless, 10-year OS for the LR cohort was 27.5% (95% confidence interval [CI]: 24.4%-30.8%) versus 14.7% (95% CI: 9.8%-20.7%, p < 0.001) for TA patients. In stratified analysis, survival benefit was statistically significant only among those with negative resection margin, no lymphovascular invasion, and Charlson-Deyo score ≤1. In multivariable Cox analysis, LR was independently associated with improved survival compared to TA (hazard ratio: 0.80; 95% CI = 0.67-0.95). CONCLUSION: LR poses a higher long-term survival benefit than TA. Prospective studies are warranted to confirm these findings. Although our study patients are a highly selected group of multifocal T2 patients, it gives us a good insight into the fact that LR provides better outcomes if a transplant option is unavailable.

Trends and disparities in access to minimally invasive distal pancreatectomy (midp): an eight-year analysis from the national cancer database.

Laparoscopic and robotic approaches to distal pancreatectomy are becoming the standard of care. The aim of our study was to evaluate the trends of utilization and disparities in access to minimally invasive approaches in distal pancreatectomy. We queried the National Cancer Database (NCDB) and analyzed all the patients who underwent distal pancreatectomy from 2010 to 2017. Patients were divided into groups of those with open distal pancreatectomy (ODP) and those with laparoscopic or robotic distal pancreatectomy (MIDP = minimally invasive distal pancreatectomy). Our outcome measures were trends of MIDP and disparities in access to MIDP. Cochran Armitage trend analysis and multivariate regression analysis were used to evaluate outcomes. A total of 13,537 patients with distal pancreatectomy were identified in the NCDB from 2010 to 2017. 7548 (55.8%) underwent ODP, while 5989 (44.2%) underwent MIDP. The MIDP rates increased from 25% in 2010 to 52% in 2017 (p < 0.01). On regression analysis, when controlled for age, gender, diagnosis, tumor size, grade, staging, and chemoradiotherapy, African American patients were 30% less likely to undergo MIDP than White (OR 0.7, 95% CI [0.5-0.8], p < 0.01). Similarly, Hispanic patients were 25% less likely to undergo MIDP than non-Hispanic patients OR 0.75, 95% CI [0.6-0.9], p = 0.02). Compared to Medicare/private insured patients, uninsured patients were 50% less likely to undergo MIDP (OR 0.5, 95% CI [0.4-0.7], p < 0.01). Based on the medium household income, compared to patients in the fourth quartile, patients in the third quartile OR 0.9, 95% CI [0.3-0.9], p = 0.03). Second OR 0.8, 95%CI [0.5-0.9], p < 0.01), first quartile OR 0.7, 95% CI [0.5-0.8], p < 0.01) were less likely to undergo MIPD as well. Utilization of MIDP has increased from one in every four patients in 2010 to every other patient in 2017. However, African Americans, Hispanics, the uninsured, and those from low-income quartiles are less likely to undergo MIDP. Efforts should be made to ensure access to minimally invasive approches are available to minorities.

Outcomes in elderly patients undergoing hepatic resection compared to liver transplant for hepatocellular carcinoma.

BACKGROUND: Hepatic resection (HR) is an excellent option for patients with hepatocellular carcinoma (HCC). For patients meeting the Milan criteria, a liver transplant (LT) is also a viable option for patients with HCC, especially those with end-stage liver disease. With increasing rates of LTs amongst the elderly, we sought to determine long-term outcomes in patients who underwent HR compared to LTs in this patient population. METHODS: We queried the national cancer database for elderly patients (≥70 years) diagnosed with HCC between 2004 and 2020. The primary outcome was overall survival (OS) computed using the Kaplan-Meier method and Cox proportional hazard regression. One-to-one propensity score matching was conducted on the basis of clinicodemographic features to account for baseline differences between patients undergoing each procedure. RESULTS: Of the 5090 patients included, 4674 (91.8%) and 416 (8.2%) patients underwent HR and LT, respectively. Compared with HR patients, patients receiving LT had better OS (p < 0.001) and greater median survival time (65.6 months HR vs. 97.9 months LT, p < 0.001). On multivariable analysis, a LT was independently associated with improved survival (adjusted hazard ratio: 0.61, 95% confidence interval: 0.50-0.76, p < 0.001). CONCLUSIONS: LT is associated with improved survival for well-selected elderly patients with HCC. Age alone should not be used as the sole parameter for the candidacy of LT in elderly patients.

Biliary Complications After Liver Transplantation in the United States: Changing Trends and Economic Implications.

BACKGROUND: Biliary complications (BCs) continue to impact patient and graft survival after liver transplant (LT), despite improvements in organ preservation, surgical technique, and posttransplant care. Real-world evidence provides a national estimate of the incidence of BC after LT, implications for patient and graft outcomes, and attributable cost not available in transplant registry data. METHODS: An administrative health claims-based BC identification algorithm was validated using electronic health records (N = 128) and then applied to nationally linked Medicare and transplant registry claims. RESULTS: The real-world evidence algorithm identified 97% of BCs in the electronic health record review. Nationally, the incidence of BCs within 1 y of LT appears to have improved from 22.2% in 2002 to 20.8% in 2018. Factors associated with BCs include donor type (living versus deceased), recipient age, diagnosis, prior transplant, donor age, and donor cause of death. BCs increased the risk-adjusted hazard ratio (aHR) for posttransplant death (aHR, 1.43; P < 0.0001) and graft loss (aHR, 1.48; P < 0.0001). Nationally, BCs requiring intervention increased risk-adjusted first-year Medicare spending by $39 710 ( P < 0.0001). CONCLUSIONS: BCs remain an important cause of morbidity and expense after LT and would benefit from a systematic quality-improvement program.

AP-1-independent NFAT signaling maintains follicular T cell function in infection and autoimmunity.

Coordinated gene expression programs enable development and function of T cell subsets. Follicular helper T (Tfh) cells coordinate humoral immune responses by providing selective and instructive cues to germinal center B cells. Here, we show that AP-1-independent NFAT gene expression, a program associated with hyporesponsive T cell states like anergy or exhaustion, is also a distinguishing feature of Tfh cells. NFAT signaling in Tfh cells, maintained by NFAT2 autoamplification, is required for their survival. ICOS signaling upregulates Bcl6 and induces an AP-1-independent NFAT program in primary T cells. Using lupus-prone mice, we demonstrate that genetic disruption or pharmacologic inhibition of NFAT signaling specifically impacts Tfh cell maintenance and leads to amelioration of autoantibody production and renal injury. Our data provide important conceptual and therapeutic insights into the signaling mechanisms that regulate Tfh cell development and function.

Outcomes after lung resection in renal transplant patients with pulmonary mucormycosis.

BACKGROUND: Pulmonary mucormycosis has been associated with high mortality (reported up to 100%) in renal transplant recipients. METHODS: This was a retrospective analysis of renal transplant patients with pulmonary mucormycosis between April 2014 and March 2020, who underwent surgical resection of the affected lung along with liposomal amphotericin therapy. Patients with lower respiratory illness features underwent chest X-ray, high-resolution computed tomography of the chest, and those with suspicious findings underwent analysis of bronchioloalveolar fluid and transbronchial lung biopsy. Patients with histological or microbiological evidence of mucormycosis were started on liposomal Amphotericin B. Tacrolimus and mycophenolate mofetil were stopped at the time of diagnosis. RESULT: Ten patients underwent combined management, while five patients were managed medically. At last follow up, seven out of ten patients (70%) who underwent combined management and two of the five patients (40%) who were managed medically, had a mean survival of 28.86 months (sd = 15.71, median = 25) and 14.17 months (sd = 12.21, median = 18), respectively, post-diagnosis of pulmonary mucormycosis. CONCLUSION: Surgical resection combined with antifungals in the perioperative period and decreased immunosuppression may improve the outcomes in renal transplant patients with pulmonary mucormycosis.

Outcome of tibio-saphanous arteriovenous fistula in patients with failed upper extremity dialysis access: A report of two cases.

Arteriovenous fistulas (AVF) are the preferred access for hemodialysis in patient with end stage renal disease. Usually, distal vessels of upper limb are preferred. There are situations in which the upper limb cannot be a site for AVFs or graft as in cases of bilateral central venous stenosis or with exhausted sites in upper limb. In these cases, lower limb AVF can be considered. Tibial-saphanous (ankle) fistula should be the preferred site over femoral AVF/graft following the principle of distal to proximal. Also, femoral AVFs are associated with more ischemic and infective complications. The present report describes successful hemodialysis in two patients with tibial-saphanous fistula a site rarely used as an option for HD access. Hemodialysis for over 1 year in one patient and 6 months in the other portrays the success of this approach.

Analysis of Organ Utilization From Deceased Organ Donation in India.

OBJECTIVES: This report presents an audit of utilization of various organs from deceased donors in different states of India over a 3-year period METHODS: Data released by the various regions on their official website was analyzed from 2015 to 2017.Regions with less than 25 donations per year were excluded while calculating utilization rates. RESULTS: Total organ donation in India had increased from 570 to 843 donations from 2015 to 2017 (47.8% increase) with southern states performing exceedingly well compared with northern states. Total organs retrieved during the 3-year period were 6659 with a 54.7% increase in organ retrieval in 2017 compared with 2015 (2592 vs 1675 respectively). The net utilization rate of kidneys was 87.35%. Total liver transplants done during this period were 1894. Net liver utilization rate was 86.81% over 3 years. Total Heart transplants during this period were 641 with net utilization rate of 28.98%. An increase in utilization rates was observed from 2015 to 2017 (19.33%-34.46%). A total of 217 lung transplants were done with net utilization rate of 8.86% with an increase in yearly utilization rate from 6.5% in 2015 to 11.97% in 2017. Total pancreas transplants remained low with 48 transplants over 3 year duration with net utilization rate of 2.25% but an increase in utilization rate was observed. (0.92% in 2015 to 2.1% in 2017). CONCLUSION: There is a significant regional variability in organ utilization in India. Evaluating and addressing the cause of high variability can further increase the transplant activity.

Risk for Delayed Graft Function in Deceased Donor Renal Transplant Patients: A Single-Center Experience From North India.

OBJECTIVES: Delayed graft function (DGF) in renal allograft transplantation refers to the need for dialysis in the first week after renal transplantation. This study analyzed the causes of DGF in deceased donor transplantation. METHODS: Data from January 2018 to July 2019 was reviewed with regard to donor and recipient characteristics such as demographics, biochemical parameters, organ dysfunction, and preterminal management. The recipients were divided into 2 groups: group I: patients without DGF and group II: patients with DGF. RESULTS: Kidneys were retrieved from 49 deceased donors (male:female = 41:8) and transplanted to 95 recipients (male:female = 60:35). Mean age of the donors and recipients was 35.34 ± 18.2 and 40.72 ± 13.30 years, respectively. The most common cause of brain death was central nervous system trauma (45 out of 49, 91%). In total, 20/95 (21%) recipients had DGF. Twelve recipients had received kidneys from donors who had circulatory arrest. Two patients were re-explored on postoperative day 1 for bleeding from renal artery anastomosis. The mean age in group I and group II was 28.65 ± 10.2 and 37.38 ± 12.28 years, respectively. The mean cold ischemia time in group I and group II was 398.73 ± 187.19 and 333.24 ± 115.49 minutes, respectively. The mean hospital stay of donor before donation in group I and group II was 4.34 ± 1.27 and 6 ± 2.95 days, respectively. The terminal donor creatinine in group I and group II was 0.88 ± 0.47 and 2.33 ± 1.73 mg/dL, respectively. CONCLUSION: DGF in deceased donor transplantation may be attributed to donation after circulatory death, prolonged donor hospital stay, high donor leukocyte count, and high terminal creatinine.

Reasons for Low Utilization of Pancreas for Transplantation From Deceased Donors: Analysis of Data From a Single Center in India.

OBJECTIVES: Although pancreas transplants were started at our center in 2014, the number of pancreases procured have remained low. This report presents an audit of donors over the past 18 months with the aim to identify factors preventing pancreas utilization. METHODS: This was a retrospective study. All deceased donors from January 2018 to July 2019 were included in this study. The medical records of deceased donors were reviewed with regard to donor characteristics such as demographics, biochemical parameters, and preterminal management. RESULTS: Organs were retrieved from 49 deceased donors over the duration of the study. Mean age of the donors was 35.34 ± 18.2 years (11 months to 72 years). Most donors were men (M:F 41:8). In total, 45/49 (92%) donors had central nervous system trauma as a cause of brain death. Out of 49, multiple abdominal organs were retrieved from 21 donors (42.8%), whereas kidneys alone were retrieved from the rest. Pancreases were retrieved from 8 donors (16.3%). Pancreases were rejected in 21 donors (42.8%) because of age limit criteria. Other reasons for refusal included donor sepsis (n = 12, 24.5%), severe hemodynamic instability (n = 5, 10.2%), donation after cardiac death (DCD) (n = 2, 4.1%), and ischemic hepatitis (n = 7, 14.3%) while 3 (6.1%) donations happened while awaiting license renewal. A suitable recipient was not available for 1 donor (2.0%). CONCLUSION: Pancreas retrieval rates remain low because of donor-related factors. Expansion of age limits and better donor management could improve pancreas transplant activity.

Experience With 15 Years of Laparoscopic Donor Nephrectomy: Review of 2500 Cases.

BACKGROUND: Laparoscopic donor nephrectomy (LDN) is considered the gold standard for live donor nephrectomies owing to lesser pain, shorter hospitalization, and earlier return to normal activities, yet it remains a technically challenging surgery. Repetition of a highly skilled task such as LDN should lead to improved performance reflected in shorter surgery times and a decrease in adverse events. METHODS: The records of over 2524 LDNs from February 2004 to June 2019 were evaluated for duration of surgery (from incision time to clamping of the renal artery) and occurrence of complications. RESULTS: The mean duration of surgery ± SD from incision to clamp time for the first 100 cases at the inception of LDN was 166.13 ± 33.28 minutes whereas it was 124.59 ± 35.91 minutes for the best 100 consecutive cases in 2015 with a decrease of 41 minutes duration of surgery from incision to artery clamping. The adverse events were accessory renal artery injury (n = 10), splenic laceration (n = 2), bowel and mesocolon injuries (n = 12), venous or arterial clip slippage (n = 4), inferior vena cava tear (n = 2) pneumothorax (during stapler application, n = 1), missing gauze counts (n = 1), chylous ascites (n = 1), ureteric thermal injury (n = 2), and renal parenchyma injury (n = 3). CONCLUSIONS: LDN is a technically demanding surgery where surgeon experience appears to affect operative metrics such as operative time. The occurrence of intraoperative complications appears to be acceptably low, although serious complications are a possibility.

Spatial and functional heterogeneity of follicular helper T cells in autoimmunity.

Follicular helper T cells provide signals that promote B cell development, proliferation, and production of affinity matured and appropriately isotype switched antibodies. In addition to their classical locations within B cell follicles and germinal centers therein, B cell helper T cells are also found in extrafollicular spaces - either in secondary lymphoid or non-lymphoid tissues. Both follicular and extrafollicular T helper cells drive autoantibody-mediated autoimmunity. Interfering with B cell help provided by T cells can ameliorate autoimmune disease in animal models and human patients. The next frontier in Tfh cell biology will be identification of Tfh cell-specific pathogenic changes in autoimmunity and exploiting them for therapeutic purposes.

A Novel Technique of Dual Kidney Transplantation (DKT) From Adult Donors.

OBJECTIVE: To discuss a novel technique of dual kidney transplantation that has not been described in literature. METHODS: Dual Kidney Transplantation (DKT) is done for kidneys from expanded criteria donors. The 3 described techniques in literature (bilateral placement, unilateral placement with separate or patch anastomosis) have some disadvantages. This newer technique describes the use of the donor iliac artery as an interposition Y graft for joining both kidneys of the dual kidney transplant. This method can overcome some of the disadvantages associated with the previously described techniques. The ureters were implanted in urinary bladder separately in one recipient and together in another recipient. RESULTS: This technique was used in 2 cases. The cold ischemia time was 275 minutes and 765 minutes, respectively while the operative time was 187 minutes and 192 minutes, respectively in the 2 patients. The first patient has creatinine of 0.83 mg/dl on last follow up at 6 months whereas the other patient has creatinine of 1.12 mg/dl at 3 months follow up. Computed tomography angiography of both the patients revealed good contrast uptake in both kidneys with no stenosis, torsion or lymphocele. CONCLUSION: The newer technique avoids scarring of both iliac fossa in DKT while reducing operative time and secondary warm ischemia time by doing a single arterial anastomosis in the recipient and allows easier placement of both kidneys in the right iliac fossa.

Clinical Profile and Outcome in Patients of Diabetic Foot Infection.

PURPOSE: The aim is to study the clinical profile and outcome of patients presenting with diabetic foot infections (DFI). METHODS: This was a prospective study recruiting patients >18 years of age, with DFI. All patients underwent a detailed history and clinical examination. Patients were classified as per the International Working Group on the Diabetic Foot -IDSA classification. The patients were followed up every month for 3 months. Clinical outcome was studied regarding the rate of amputations, readmissions, and mortality. RESULTS: There were 65 patients with a mean age of 58.49 ± 11.04 years with male predilection (83.08%). Mean duration of diabetes mellitus was 12.03 ± 6.96 years. Ulcer (92.31%) and discharge (72.31%) were the most common presenting complaints. Monomicrobial growth was present in 36 patients (55.38%). Majority of isolates were Gram-negative (71.43%). The most common isolates were Escherichia coli and Staphylococcus aureus (28.57% each). Mild, moderate, and severe DFI was present in 40%, 47.69%, and 12.31% of patients, respectively. Severe DFI was associated with poor ulcer healing (P = 0.02) and higher number of major amputations (P < 0.001). Minor amputations were most commonly associated with moderate and severe DFI. Severe DFI had the highest number of readmissions (P = 0.04). Patients undergoing minor amputations had a significant association with area of ulcer (P < 0.001). CONCLUSION: This study shows the predominance of monomicrobial growth and Gram-negative organisms in diabetic foot patients. With increase in the severity of DFI, there was increased rate of hospital readmissions, amputations (major and minor), and mortality. Dimensions of ulcer may have a bearing on rate of minor amputations.

"Swirl Sign" in Extradural Hematoma.

"Swirl sign" is a relatively uncommon sign, seen on noncontrast CT scan in patients of head trauma who develop extradural hematoma. It has 2 components: hyperacute, which represents ongoing active intracranial bleed, and acute, which comprises surrounding hyperattenuated clotted blood. The importance of early identification of this sign by surgeons and aggressive surgical management might have a bearing on the prognosis and survival of the patients, as emphasized here by 2 clinical scenarios. The clinical implication is that identification of the swirl sign suggests expanding extradural hematoma with ongoing active bleed, warranting aggressive surgical management.

Chylous Ascites: Complication of Laparoscopic Donor Nephrectomy. Case Report and Review of Literature.

BACKGROUND: Chylous ascites (CA) is an extremely rare complication after laparoscopic donor nephrectomy (LDN). It can increase the hospital stay, morbidity in postoperative period and thus negating the benefits of laparoscopic surgery. Most of the cases were managed conservatively, but surgical intervention may be occasionally required. This report describes the importance of accurate localization of the leaking chyle duct and its repair by endosuturing in a renal donor not responding to conservative treatment. METHODS: A comprehensive review of literature regarding this rare complication after LDN was performed with Pubmed/Medline and Google Scholar using "chyle," "complications," and "laparoscopic donor nephrectomy" as keywords. The demographic profile and management of patients is discussed in detail. The various surgical modalities used to manage these patients are described. RESULTS: Fifty-four cases of chyle leak/ascites have been reported after LDN in literature to date. Around 77% donors with CA could be successfully managed conservatively with dietary measures and total parenteral nutrition. Surgical intervention was required in nearly 23% donors ranging from clip application, use of argon coagulation, endosuturing with application of glue after 36.1 ± 19.07 days of failed conservative treatment. Donors with massive ascites or requiring frequent large-volume paracentesis on conservative treatment are likely to require surgical therapy. The present case was successfully managed with laparoscopic endosuturing and has no recurrence at 6 month follow-up. CONCLUSIONS: Chylous ascites is a rare complication after donor nephrectomy in experienced centers. Although conservative management remains the first line of treatment, early surgical treatment shall be undertaken in cases of massive ascites.

Ameboma of Colon Simulating Colonic Adenocarcinoma.

Amebiasis is common in tropical and developing countries with variable symptoms. Ameboma of the colon occurs rarely due to the annular growth of granulation tissue and can present as mass lesion simulating colonic carcinoma in elderly individuals. Due to diagnostic dilemma or in case of complications, for example, acute intestinal obstruction, perforation, or bleeding per rectum, the patient requires urgent surgical exploration and final diagnosis is made on histopathological examination.

Disruption of Pathogenic Cellular Networks by IL-21 Blockade Leads to Disease Amelioration in Murine Lupus.

Systemic lupus erythematosus (lupus) is characterized by autoantibody-mediated organ injury. Follicular Th (Tfh) cells orchestrate physiological germinal center (GC) B cell responses, whereas in lupus they promote aberrant GC responses with autoreactive memory B cell development and plasma cell-derived autoantibody production. IL-21, a Tfh cell-derived cytokine, provides instructional cues for GC B cell maturation, with disruption of IL-21 signaling representing a potential therapeutic strategy for autoantibody-driven diseases such as systemic lupus erythematosus. We used blockade of IL-21 to dissect the mechanisms by which this cytokine promotes autoimmunity in murine lupus. Treatment of lupus-prone B6.Sle1.Yaa mice with an anti-IL-21 blocking Ab reduced titers of autoantibodies, delayed progression of glomerulonephritis and diminished renal-infiltrating Tfh and Th1 cells, and improved overall survival. Therapy inhibited excessive accumulation of Tfh cells coexpressing IL-21 and IFN-γ, and suppressed their production of the latter cytokine, albeit while not affecting their frequency. Anti-IL-21 treatment also led to a reduction in GC B cells, CD138hi plasmablasts, IFN-γ-dependent IgG2c production, and autoantibodies, indicating that Tfh cell-derived IL-21 is critical for pathological B cell cues in lupus. Normalization of GC responses was, in part, caused by uncoupling of Tfh-B cell interactions, as evidenced by reduced expression of CD40L on Tfh cells and reduced B cell proliferation in treated mice. Our work provides mechanistic insight into the contribution of IL-21 to the pathogenesis of murine lupus, while revealing the importance of T-B cellular cross-talk in mediating autoimmunity, demonstrating that its interruption impacts both cell types leading to disease amelioration.