Local Plasma Cells Research Articles

Immunological memory diversity in the human upper airway.

The upper airway is an important site of infection, butimmune memory in the human upper airway is poorly understood, with implications for COVID-19 and many other human diseases1-4. Here we demonstrate that nasal and nasopharyngeal swabs can be used to obtain insights into these challenging problems, and define distinct immune cell populations, including antigen-specific memory Bcells and T cells, in two adjacent anatomical sites in the upper airway. Upper airway immune cell populations seemed stable over time in healthy adults undergoing monthly swabs for more than 1 year, and prominent tissue resident memory T (TRM)cell and B (BRM) cellpopulations were defined. Unexpectedly, germinal centre cells were identified consistently in many nasopharyngeal swabs. In subjects with SARS-CoV-2 breakthrough infections, local virus-specific BRMcells, plasma cells and germinal centre B cells were identified, with evidence of local priming and an enrichment of IgA+ memory B cells in upper airway compartments compared with blood. Local plasma cell populations were identified with transcriptional profiles of longevity. Local virus-specific memory CD4+ TRM cellsand CD8+ TRM cellswere identified, with diverse additional virus-specific T cells. Age-dependent upper airway immunological shifts were observed. These findings provide new understanding of immune memory at a principal mucosal barrier tissue in humans.

Increased frequency of oral plasma cell mucositis/plasma cell gingivitis after the COVID-19 pandemic: a 23-year retrospective analysis and review of diagnostic challenges relating to this condition

Oral plasma cell mucositis (PCM) or localized plasma cell gingivitis (PCG) is an idiopathic inflammatory condition often associated with hypersensitivity reactions. This study aimed to evaluate the frequency and features of PCM/PCG in a large biopsy service over a time period of more than 20 years. The biopsy archives at University of Florida College of Dentistry were searched from 2000 through the first quarter of 2023 for cases of oral PCM or PCG. Case data were aggregated and analyzed. A total of 107 cases were included. Between 2000 and 2019, PCM/PCG was diagnosed in 0.03% of all biopsy cases. Starting in 2020 through 2023, the percentage of biopsies diagnosed as PCM/PCG increased threefold to 0.10% of all biopsy cases, and the mean patient age increased by 3 years. There were no statistically significant differences between cases diagnosed from 2000 to 2019 and those from 2020 to 2023 regarding age, sex, location, or histology. A significant increase in PCM/PCG was identified in this study at one institution coinciding with the start of the COVID-19 pandemic. Further investigation is recommended to determine if this is a widespread phenomenon and identify possible etiologic mechanisms.

Solitary Bone Plasmacytoma Mimicking Oral Cavity Neoplasm – A Rare Case

Plasmacytomas are localized monoclonal plasma cell lesions with no evidence of systemic involvement which are divided into solitary bone plasmacytoma (SBP) and extra-medullary plasmacytoma (EMP). The diagnosis of plasmacytomas (PCM) in the oral regions is challenging given the atypical clinical manifestations and low frequency. Here, we report an extremely rare case of plasmacytoma in an elderly male which initially appeared to be arising from the left buccal mucosa on clinical examination but after radiological imaging and intra-operative findings, the epicentre was found to be in the left infratemporal fossa (ITF). The patient underwent en-bloc compartment resection with high clearance of the ITF which proved to be an effective management strategy. It is crucial for the head and neck surgeon to be aware of the solitary bone plasmacytoma in the oral and maxillofacial region in order to identify it early and provide these patients with the best care possible before complications arise.

Survival trends and prognostic factors for patients with extramedullary plasmacytoma: A population-based study.

Extramedullary plasmacytoma (EMP) is a localized plasma cell neoplasm that originates from tissues other than bone. The survival trends and prognostic factors of patients with EMP in recent years remain unreported. We used the SEER databases to extract the data. Survival curves were calculated using the Kaplan-Meier method and a nomogram was created based on the Cox's proportional hazards model. A total of 1676 cases of EMP were identified. Patients in period-2 (2008-2016) show similar survival (p=0.8624) to those in period-1(1975-2007). Age, gender, race, and sites were prognostic of patient outcomes. And the use of surgery was associated with improved survival. The patients were randomly assigned to the training cohort and the validation cohort in a ratio of 2:1. Four factors including age, gender, race, and sites were identified to be independently predictive of the overall survival of patients with EMP. A prognostic model (EMP prognostic index, EMP-PI) comprising these four factors was constructed. Within the training cohort, three risk groups displayed significantly different 10-year survival rates: low-risk (73.0%, [95%CI 66.9-78.2]), intermediate-risk (39.3%, [95%CI 34.3-44.3]), and high-risk (22.6%, [95%CI 15.3-30.9]) (p<0.0001). Three risk groups were confirmed in the internal validation cohort. We also constructed a 5-factor nomogram based on multivariate logistic analyses. The survival of patients with EMP did not improve in recent years. The EMP-PI will facilitate the risk stratification and guide the risk-adapted therapy in patients with EMP.

Integrated single cell and spatial transcriptomics reveal autoreactive differentiated B cells in joints of early rheumatoid arthritis

B cells play a significant role in established Rheumatoid Arthritis (RA). However, it is unclear to what extent differentiated B cells are present in joint tissue already at the onset of disease. Here, we studied synovial biopsies (n = 8) captured from untreated patients at time of diagnosis. 3414 index-sorted B cells underwent RNA sequencing and paired tissue pieces were subjected to spatial transcriptomics (n = 4). We performed extensive bioinformatics analyses to dissect the local B cell composition. Select plasma cell immunoglobulin sequences were expressed as monoclonal antibodies and tested by ELISA. Memory and plasma cells were found irrespective of autoantibody status of the patients. Double negative memory B cells were prominent, but did not display a distinct transcriptional profile. The tissue architecture implicate both local B cell maturation via T cell help and plasma cell survival niches with a strong CXCL12–CXCR4 axis. The immunoglobulin sequence analyses revealed clonality between the memory B and plasma cell pools further supporting local maturation. One of the plasma cell-derived antibodies displayed citrulline autoreactivity, demonstrating local autoreactive plasma cell differentiation in joint biopsies captured from untreated early RA. Hence, plasma cell niches are not a consequence of chronic inflammation, but are already present at the time of diagnosis.

Successful Vaccination of Patients with History of Severe Anaphylactic Reaction with Pfizer-Biotech COVID-19 Vaccine

Plasmacytomas are localized tumors of monoclonal plasma cells, typically affecting the axial skeleton and present as solitary bone lesions known as solitary bone plasmacytomas (SBP). Another type of plasmacytomas are extramedullary plasmacytomas (EP) that are localized plasma cell neoplasms affecting the soft tissues such as skin, brain lymph nodes etc. These tumors are account for 5-10% of all plasma cell disorders and among these tumors a rare entity is a multiple solitary plasmacytoma (MSP). MSPs are rare and account for only 5% of all SBPs. MSP presents with multiple SBPs with or without EPs with no bone marrow involvement as multiple myeloma. Literature is limited on MSP as it is a rare diagnosis. Here, we present a case of a 64-year-old male who presented with shoulder pain after a fall, found to have an SBP of the right shoulder, SBP of left femur and a left hypopharyngeal EP. The tumors were excised and he was treated with 6 cycles of bortezomib and dexamethasone. After chemotherapy and radiation patient showed good response and remained in remission on follow up.

Multiple Solitary Plasmacytoma: A Rare Presentation

Plasmacytomas are localized tumors of monoclonal plasma cells, typically affecting the axial skeleton and present as solitary bone lesions known as solitary bone plasmacytomas (SBP). Another type of plasmacytomas are extramedullary plasmacytomas (EP) that are localized plasma cell neoplasms affecting the soft tissues such as skin, brain lymph nodes etc. These tumors are account for 5-10% of all plasma cell disorders and among these tumors a rare entity is a multiple solitary plasmacytoma (MSP). MSPs are rare and account for only 5% of all SBPs. MSP presents with multiple SBPs with or without EPs with no bone marrow involvement as multiple myeloma. Literature is limited on MSP as it is a rare diagnosis. Here, we present a case of a 64-year-old male who presented with shoulder pain after a fall, found to have an SBP of the right shoulder, SBP of left femur and a left hypopharyngeal EP. The tumors were excised and he was treated with 6 cycles of bortezomib and dexamethasone. After chemotherapy and radiation patient showed good response and remained in remission on follow up

Free light chains as an emerging biomarker in saliva: Biological variability and comparisons with salivary IgA and steroid hormones

BackgroundSalivary free light chains (FLCs) are an emerging biomarker in health and behavioural research. However, little is known regarding biological variability of salivary FLCs and how they relate to other established salivary biomarkers. This study aimed to investigate the diurnal and day-to-day variation of salivary FLCs and their relationship with salivary IgA and steroid hormones. MethodsA total of 46 healthy adults participated in studies exploring the biological variability of FLCs. Diurnal variation was investigated by collecting saliva samples immediately upon waking, 0.5 h, 3 h, 6 h, 9 h and 14 h post-waking. Saliva samples were assessed for FLCs, IgA, cortisol and dehydroepiandrosterone (DHEA). Between-day variation in FLCs and IgA was assessed by collecting saliva samples immediately upon waking for seven consecutive days. Participants underwent a dental examination to exclude oral health as a potential confounding variable. Within and between-person day-to day variation was explored in relation to a range of different factors: awakening time, sleep, exercise, well-being and alcohol consumption. ResultsSalivary secretion rates of FLCs decreased following waking and up to 3 h post-waking and then plateaued. This same pattern was observed for IgA. DHEA was stable upon waking and higher levels were seen in the morning with significantly lower levels thereafter. Cortisol levels significantly increased 0.5 h post-waking then continued to decline across the day. FLCs were significantly correlated with IgA but not cortisol or DHEA. Both FLCs and IgA parameters showed day-to-day variability, with coefficients of variation ≥ 40%. Earlier waking time was significantly correlated with higher FLC and IgA secretion rates. Inter-person differences in saliva parameter variability were observed but the degree of variation in FLCs and IgA was related within person. Inter-person day-to-day variation appeared to be uninfluenced by lifestyle or behavioural factors. ConclusionsSaliva FLCs secretion exhibits diurnal fluctuation that mirrors IgA fluctuation. Findings strongly indicate salivary FLC secretion is orchestrated by local plasma cells. FLCs and IgA both showed notable variability day-to-day, which was similar within person and influenced by awakening time. FLCs offer a promising adjunct to IgA in the measurement of oral immune activation.

Migrant memory B cells secrete luminal antibody in the vagina.

Antibodies secreted into the mucosal barriers serve to protect the host from a variety of pathogens, and are the basis for successful vaccines1. In type I mucosa such as the intestinal tract, dimeric IgA secreted by local plasma cells is transported through polymeric Ig receptors (pIgR)2, and mediates robust protection against viruses in the vaccinees3,4. However, due to the paucity of pIgR and plasma cells, how and whether antibodies are delivered to the type II mucosa represented by the lower female reproductive tract (FRT) lumen remains unclear. Here, using genital herpes infection in mice, we show that primary infection does not establish plasma cells in the lamina propria of FRT. Instead, upon secondary challenge with herpes simplex virus 2 (HSV-2), circulating memory B cells that enter the FRT serve as the source of rapid and robust antibody secretion into the FRT lumen. CD4 tissue-resident memory T cells (TRM) secrete interferon gamma (IFN-γ), which induces expression of chemokines including CXCL9 and CXCL10. Circulating memory B cells are recruited to the vaginal mucosa in CXCR3-dependent manner, and secrete virus-specific IgG2b, IgG2c and IgA into the FRT lumen. These results reveal circulating memory B cells as a rapidly inducible source of mucosal antibodies for the FRT.

PB2108 CIRCULATING PLASMA CELLS: AN APPROACH BASED ON NEXT GENERATION FLOW TOOLS IN MONOCLONAL GAMMAPATHIES

Background:Peripheral blood (PB) is an accessible tissue to study the traffic of all types and subsets of cells. The frequency of PB involvement depends on the sensitivity of the methods used. Next Generation Flow (NGF)‐MM MRD Euroflow workflow provides a high specific, sensitive and applicable method to detect plasma cells in multiple myeloma (MM) patients after therapy. This Standard Operation Procedure (SOP) can be used to increase the sensibility of circulating plasma cells detection. Taking this into account, we investigated the frequency and number of circulating tumor plasma cells in PB of newly diagnosed patients with localized and systemic plasma cell neoplasms (PCN) using NGF.Aims:to detect, identificate and quantificate both compartments, pathologycal and normal circulating plasma cells in patients with monoclonal gammapathies.MethodsOverall, 26 samples ‐13 bone marrow (BM) and 13 paired PB samples‐ from 13 adult patients (5 males and 8 females; median age of 72 years, ranging from 42 to 85 years) with newly diagnosed PCN, were studied. In parallel, 5 PB samples from healthy donors with ages and sex similar as the patients were also investigated. Patients were classified according to the International Myeloma Working Group (IMWG) criteria into: 6 monoclonal gammopathy of undetermined significance (MGUS), 2 smoldering multiple myeloma (SMM), 5 MM patients. PB (range: 5.2 mL–10.7 mL) samples were processed following EuroFlow Bulk Lysis Standard Operating Protocols and stained with EuroFlow‐MM MRD panel 2‐tube/8‐color. A range of 5.9 × 106‐12.7 × 106 events were measured in PB samples using a FACSCanto II (BD Biosciences, San Jose, USA) flow cytometer. Information acquired were analyzed using Infinicyt software 2.0 (Cytognos, Salamanca, España). Serum Free Light Chains Assay (Binding Site) in SPAPLus platform.Results:In all newly diagnosed PCN patient and healthy donor, circulating normal plasma cells were detected in PB (0,00103% &gt; 0.3818%; 0,060 PC/uL‐1,510 PC/uL). Circulating tumoral plasma cells were detected in PB of all MM (100%) and SMM (100%) patients studied. Meanwhile, in only one case of the total of MGUS patients CTPC were identified. Free light‐chains (FLC) ratio, pathologycal/normal, in MGUS ranged between 1.1 to 3.2 and in the MM cases were &gt; 370. Circulating tumoral plasma cells showed an immunophenotype profile similar to their partner in BM. Even though, our number of patients was very low (total = 13) we found lower fluorescense intensity level in specifics markers such as: CD138, CD38 and CD56 in circulating tumoral plasma cells respect to BM.Summary/Conclusion:The EuroFlow NGF‐MM MRD panel and workflow show high sensitivity to detect CPC in PB of every newly diagnosed MM and SMM patient. Nevertheless, the majority of MGUS cases showed no detectable CTPC in PB, but these findings are correlated with a low FLC ratio, suggesting that these MGUS cases can be associated with a lower risk of malignant progression.

Memory B cell recruitment to the vaginal mucosa is required for luminal antibody secretion

Abstract Antibodies secreted into the mucosal barriers serve to protect the host from a variety of pathogens, and are the basis for successful vaccines. In type I mucosa such as the intestinal tract, dimeric IgA secreted by local plasma cells is transported through polymeric Ig receptors (pIgR). However, due to the paucity of pIgR and plasma cells, how and whether antibodies are delivered to the type II mucosa represented by the lower female reproductive tract (FRT) lumen remains unclear. Here, using genital herpes infection in mice, we show that primary infection does not establish plasma cells in the lamina propria of FRT. Instead, upon secondary challenge with herpes simplex virus 2 (HSV-2), circulating memory B cells that enter the FRT serve as the source of rapid and robust antibody secretion into the FRT lumen. CD4 tissue-resident memory T cells (TRM) secrete interferon gamma (IFN-γ), which induces expression of chemokines including CXCL9 and CXCL10. Circulating memory B cells are recruited to the vaginal mucosa in CXCR3-dependent manner, and secrete virus-specific IgG2b, IgG2c and IgA into the FRT lumen. These results reveal circulating memory B cells as a rapidly inducible source of mucosal antibodies for the FRT.

Next generation flow for minimally-invasive blood characterization of MGUS and multiple myeloma at diagnosis based on circulating tumor plasma cells (CTPC)

Here, we investigated for the first time the frequency and number of circulating tumor plasma cells (CTPC) in peripheral blood (PB) of newly diagnosed patients with localized and systemic plasma cell neoplasms (PCN) using next-generation flow cytometry (NGF) and correlated our findings with the distinct diagnostic and prognostic categories of the disease. Overall, 508 samples from 264 newly diagnosed PCN patients, were studied. CTPC were detected in PB of all active multiple myeloma (MM; 100%), and smoldering MM (SMM) patients (100%), and in more than half (59%) monoclonal gammopathy of undetermined significance (MGUS) cases (p <0.0001); in contrast, CTPC were present in a small fraction of solitary plasmacytoma patients (18%). Higher numbers of CTPC in PB were associated with higher levels of BM infiltration and more adverse prognostic features, together with shorter time to progression from MGUS to MM (p <0.0001) and a shorter survival in MM patients with active disease requiring treatment (p ≤ 0.03). In summary, the presence of CTPC in PB as assessed by NGF at diagnosis, emerges as a hallmark of disseminated PCN, higher numbers of PB CTPC being strongly associated with a malignant disease behavior and a poorer outcome of both MGUS and MM.

A rare diagnosis of nasal mass: extramedullary plasmacytoma

&lt;p&gt;Extramedullary plasmacytomas (EMPs) are localized plasma cell neoplasms that occur within the soft tissue. Solitary plasmacytoma of the head and neck is a rare disease entity. They account for 1–2% of all plasma cell growths and have a great predilection for the upper respiratory tract. Males are more frequently affected during the fifth and sixth decades of life. We report a case of maxillary sinus plasmacytoma in an elderly man. Complete resolution of the tumour was seen with radiotherapy. &lt;/p&gt;

Pattern of care and impact of prognostic factors on the outcome of head and neck extramedullary plasmacytoma: a systematic review and individual patient data analysis of 315 cases.

Head and neck extramedullary plasmacytoma is a rare localized plasma cell neoplasm. We intended to perform this review of the published literature to assess the demographic profile, pattern of care and survival outcomes. Two authors independently searched PubMed, Google search and Cochrane library for eligible studies from 1950 till July 1, 2016, published in English language. Median age of the cohort was 57years (range 11-85). Site-wise distributions were paranasal sinuses 22.3% (70), nasal cavity 17.5% (55), nasopharynx 10.8% (34). Median size of SEMP was 3cm (range 0.3-12cm). Treatment distribution was radiotherapy (RT) in 52% (164), surgery (S) 19% (60), chemotherapy (C) 5% (16), S + RT 23.49% (74),CRT 1.9% (6), S + C 0.6% (2), S + RT + C 0.95% (3).Radiation was used as a modality in 78.4%(247), surgery in 44.1%(139), chemotherapy in 4.8%(15). Median radiation dose used was 45Gy with range 20-61Gy. Median overall survival (OS) was 40months (range 0.5-298). Median local progression-free survival was 36months (range 0-298). Median myeloma relapse-free survival was 36months (range 0.5-298). Five- and 10-year OS was 78.33 and 68.61%. Five-year cause-specific survival (CSS) and 10-year CSS was 90.15 and 83.31%. Five-year LPFS was 94.78%, and 10-year LPFS was 88.43%. Five-year myeloma progression-free survival was 84.46%, and 10-year myeloma PFS was 80.44%. The factors associated with risk of local relapse were site of disease (sinonasal), secretory EMP, type of treatment received (surgery + RT > RT alone > surgery on univariate analysis). Risk factors for myeloma relapse were coexisting diseases, site of disease (sinonasal), bony erosion, size of lesion > 5cm and type of treatment received on univariate analysis. Our study shows that combined modality S + RT is superior compared to uni-modality in preventing local recurrence. Radiation dose of 45Gy is optimal. Nodal irradiation has no impact on local recurrence.

Solitary plasmacytoma: population-based analysis of survival trends and effect of various treatment modalities in the USA

BackgroundSolitary plasmacytoma (SP) is a localized neoplastic plasma cell disorder with an annual incidence of less than 450 cases. Given the rarity of this disorder, it is difficult to conduct large-scale population studies. Consequently, very limited information on the disorder is available, making it difficult to estimate the incidence and survival rates. Furthermore, limited information is available on the efficacy of various treatment modalities in relation to primary tumor sites.MethodsThe data for this retrospective study were drawn from the Surveillance, Epidemiology and End Results (SEER) database, which comprises 18 registries; patient demographics, treatment modalities and survival rates were obtained for those diagnosed with SP from 1998 to 2007. Various prognostic factors were analyzed via Kaplan-Meier analysis and log-rank test, with 5-year relative survival rate defined as the primary outcome of interest. Cox regression analysis was employed in the multivariate analysis.ResultsThe SEER search from 1998 to 2007 yielded records for 1691 SP patients. The median age at diagnosis was 63 years. The patient cohort was 62.4% male, 37.6% female, 80% Caucasian, 14.6% African American and 5.4% other races. Additionally, 57.8% had osseous plasmacytoma, and 31.9% had extraosseous involvement. Unspecified plasmacytoma was noted in 10.2% of patients. The most common treatment modalities were radiotherapy (RT) (48.8%), followed by combination surgery with RT (21.2%) and surgery alone (11.6%). Univariate analysis of prognostic factors revealed that the survival outcomes were better for younger male patients who received RT with surgery (p < 0.05). Additionally, patients who received neoadjuvant RT had increased survival rates compared to those receiving adjuvant RT (86% vs 73%, p < 0.05). Furthermore, the analyses revealed that 5-year survival rates for patients with axial plasmacytoma were superior when RT was combined with surgery (p < 0.05). In the multivariate analysis, age <60 years and treatment with either RT or surgery showed superior survival rates. Progression to multiple myeloma (MM) was noted in 551 patients. Age >60 years was associated with a lower 5-year survival in patients who progressed to MM compared to those who were diagnosed initially with MM (15.1 vs 16.6%). Finally, those who received RT and progressed to MM still had a higher chance of survival than those who were diagnosed with MM initially and treated with RT/surgery (21.8% vs 15.9%, p < 0.05).ConclusionsA review of the pertinent literature indicates that we provided the most comprehensive population-based analysis of SP to date. Moreover, our study contributes to the establishment of the optimal SP treatment modality, as RT is the favored option in frontline settings. Consensus is currently lacking regarding the benefits of combined treatment including surgery. Thus, the findings reported here elucidate the role of primary treatment modalities while also demonstrating the quantifiable benefits of combining RT with surgery in relation to different primary tumor sites. While our results are promising, they should be confirmed through further large-scale randomized studies.

Comparison of the early period effects of bone marrow-derived mesenchymal stem cells and platelet-rich plasma on the Achilles tendon ruptures in rats

ABSTRACTIntroduction: This study aims to histopathologically, biomechanically, and immunohistochemically compare the fourth-week efficiencies of local platelet-rich plasma (PRP) and bone marrow-derived mesenchymal stem cell (rBM-MSC) treatments of the Achilles tendon ruptures created surgically in rats. Materials and Methods: The study included 35 12-month-old male Sprague Dawley rats, with an average weight of 400–500 g. Five rats were used as donors for MSC and PRP, and 30 rats were separated into MSC, PRP, and control groups (n = 10). The Achilles tendons of the rats were cut transversely, the MSC from bone marrow was administered to the MSC group, the PRP group received PRP, and the control group received physiological saline to create the same surgical effect. In previous studies, it was shown that this physiological saline does not have any effect on tendon recovery. Thirty days after the treatment, the rats were sacrificed and their Achilles tendons were examined histopathologically, immunohistochemically, and biomechanically. Results: The use of rBM-MSC and PRP in the Achilles tendon ruptures when the tendon is in its weakest phase positively affected the recovery of the tendon in histopathologic, immunohistochemical, and biomechanical manners compared to the control group (p < 0.05). While the levels of pro-inflammatory cytokines TNF-α, IFNγ, and IL 1β were significantly low, the levels of anti-inflammatory cytokines and growth factors playing key roles in tendon recovery, such as IL2, VEGF, transforming growth factor-beta, and HGF, were significantly higher in the MSC group than those of the PRP and control groups (p < 0.05). In the MSC group, the (mm) value was significantly higher (p ˂ 0.05) than that in the PRP and control groups. Conclusion: rBM-MSC and PRP promote the recovery of the tendon and increase its structural strength. The use of PRP and MSC provides hope for the treatment of the Achilles tendon ruptures that limit human beings’ functionalities and quality of life, particularly for athletes. It is thought that the use of MSC can be more effective for tendon healing; hence, more extensive and advanced studies are needed on this topic.

Solitary plasmocytoma: 19-year retrospective study and review of the literature

Solitary Plasmacytoma (SP) is a rare plasma cell dyscrasia characterized by localized plasma cell infiltration. Radiotherapy is recommended as the treatment of choice. Epidemiological data is important to evaluate the effectiveness of treatment and the progression to Multiple Myeloma (MM). We described the clinical features and follow-up of 32 patients with SP treated with radiotherapy as primary treatment at our Department of Radiotherapy and we reviewed the literature on prognostic factors of progression to MM. Ninety percent of patients (71% complete response and 19% partial response) responded to treatment. Fourteen patients progressed to MM with a median time of progression of 16, 9 months. With a median follow-up of 40 months, the 5 and 10-year estimated Overall Survey (OS) was 62, 6% and 47, 7% respectively. Predictive factors of progression are still controversial. New factors are emerging in the fields of pathology, imagiology and immunology and thus we wait longer follow-up to confirm their predictive value. SP is highly radiosensitive and radiotherapy combines excellent control rates with minimal toxicity. However, it is a heterogeneous disease and approximately half of the patients will progress to MM. Identifying the patients more likely to progress would allow us to treat them in a different way.

Immunoglobulin A as an anti-inflammatory agent.

Immunoglobulin A as an anti-inflammatory agent.

Does disease-irrelevant intrathecal synthesis in multiple sclerosis make sense in the light of tertiary lymphoid organs?

Although partly disease-irrelevant, intrathecal immunoglobulins (Ig) synthesis is a typical feature of multiple sclerosis (MS) and is driven by the tertiary lymphoid organs (TLO). A long-known hallmark of this non-specific intrathecal synthesis is the MRZ pattern, an intrathecal synthesis of Ig against measles, rubella, and zoster viruses. This non-specific intrathecal synthesis could also be directed against a wide range of pathogens. However, it is highly problematic since brain TLO should not be able to drive the clonal expansion of lymphocytes against alien antigens that are thought to be absent in MS brain. We propose to explain the paradox of non-specific intrathecal synthesis by discussing the natural properties of TLO. In fact, besides local antigen-driven clonal expansion, circulating plasmablasts and plasma cells (PC) are non-specifically recruited from blood and gain access to survival niches in the inflammatory CNS. This mechanism, which has been described in other inflammatory disorders, takes place in the TLO. As a consequence, PCs recruited in brain mirror the individual’s history of immunization and intrathecal synthesis of IgG in MS may target a broad range of common infectious agents, a hypothesis in line with epidemiological data. Moreover, the immunization schedule and its timing may interfere with PC recruitment. If this hypothesis is correct, the reaction against EBV appears paradoxical: although early infection of MS patients is systematic, intrathecal synthesis is far lower than expected, suggesting a crucial interaction between MS onset and timing of EBV infection. A growing body of evidence suggests that the non-specific intrathecal synthesis observed in MS is also common in many chronic CNS inflammatory disorders. Assuming that cortical TLO in MS are associated with typical sub-pial lesions, we have coined the concept of “TLO-pathy” to describe these lesions and take examples of them from non-MS disorders. Lastly, we propose that intrathecal synthesis could be considered a strong hallmark of CNS TLO and might be used to monitor future TLO-targeted therapies.

Extramedullary plasmacytoma of the thyroid: report of a rare case.

TO THE EDITOR: Extramedullary or extra-osseous plasmacytomas (EMP/EOP) are localized plasma cell neoplasms that arise in tissues other than bone. EMP comprises 3-5% of all plasma cell neoplasms. The upper respiratory tract and the oral cavity are the most common sites for EMP [1], and the thyroid gland is one of the rare sites for this neoplasm. Here, we report a case of EMP of the thyroid in a 53-year-old male who presented to the surgery outpatient department (OPD) with a left-sided thyroid swelling of six months duration.