Human Lymphatic System Research Articles

Mapping the Anatomy of the Human Lymphatic System.

While substantial anatomical study has been pursued throughout the human body, anatomical study of the human lymphatic system remains in its infancy. For microsurgeons specializing in lymphatic surgery, a better command of lymphatic anatomy is needed to further our ability to offer surgical interventions with precision. In an effort to facilitate the dissemination and advancement of human lymphatic anatomy knowledge, our teams worked together to create a map. The aim of this paper is to present our experience in mapping the anatomy of the human lymphatic system. Three steps were followed to develop a modern map of the human lymphatic system: (1) identifying our source material, which was "Anatomy of the human lymphatic system," published by Rouvière and Tobias (1938), (2) choosing a modern platform, the Miro Mind Map software, to integrate the source material, and (3) transitioning our modern platform into The Human BioMolecular Atlas Program (HuBMAP). The map of lymphatic anatomy based on the Rouvière textbook contained over 900 data points. Specifically, the map contained 404 channels, pathways, or trunks and 309 lymph node groups. Additionally, lymphatic drainage from 165 distinct anatomical regions were identified and integrated into the map. The map is being integrated into HuBMAP by creating a standard data format called an Anatomical Structures, Cell Types, plus Biomarkers table for the lymphatic vasculature, which is currently in the process of construction. Through a collaborative effort, we have developed a unified and centralized source for lymphatic anatomy knowledge available to the entire scientific community. We believe this resource will ultimately advance our knowledge of human lymphatic anatomy while simultaneously highlighting gaps for future research. Advancements in lymphatic anatomy knowledge will be critical for lymphatic surgeons to further refine surgical indications and operative approaches.

An advanced 3D lymphatic system for assaying human cutaneous lymphangiogenesis in a microfluidic platform

The human cutaneous lymphatic system strictly controls lymphatic functions by coordinating with skin cells. The lymphatic system plays important roles in removing cell waste, residual proteins, various antigens, and immune cells from tissues to maintain homeostasis and activate the immune system through the drainage of interstitial fluid1,2. The skin protects our body from external stimuli such as pathogens through the cutaneous lymphatic system3,4. Herein, to develop an in vitro human cutaneous lymphatic model, we present two 3D microfluidic platforms: a lymphangiogenesis model with a precollecting lymphatic vessel-like structure and an advanced lymphangiogenesis model with a functional cutaneous barrier and a precollecting lymphatic vessel-like structure. In addition, we rapidly analyzed prolymphangiogenic effects using methods that incorporate a high-speed image processing system and a deep learning-based vascular network analysis algorithm by 12 indices. Using these platforms, we evaluated the pro-lymphangiogenic effect of Lymphanax, a natural product derived from fresh ginseng. As a result, we demonstrated that Lymphanax induces robust lymphangiogenesis without any structural abnormalities. In conclusion, we suggest that these innovative platforms are useful for studying the interaction between the skin and lymphatic system as well as evaluating the prolymphangiogenic effects of drugs and cosmetics.

A Review of Bed Nets Usage and Sewerage Conditions as Risk Factors for Lymphatic Filariasis in Developing Countries

Introduction: Lymphatic filariasis, a neglected tropical disease (NTD), is a parasitic disease caused by microscopic worms that live only in the human lymphatic system. Mosquitoes, as vectors of lymphatic filariasis, play an important role in the prevention of this disease. The aim of this study was to identify agent, vector, and physical environment risk factors for filariasis in developing countries through a literature review. Discussion: This study was conducted using the narrative literature review method. The main sources for this study were articles from Google Scholar, Research Gate, PubMed, Springer, Scopus, and DOAJ databases. The criteria for articles were published between 2012 and 2022, observational studies including cross-sectional, case-control, and cohort designs, open access, and articles were organized according to STROBE guidelines. This study showed that from a total of 100 articles found, 14 articles met the predetermined criteria. Wuchereria bancrofti is the most common agent of filariasis. Culex and Anopheles are the vectors. The presence of bed nets and sewerage conditions were physical environment risk factors for filariasis in developing countries. Conclusion: Prevention of filariasis can be achieved by using mosquito nets or insect repellent when sleeping at night. In addition, open drains should be cleaned regularly to prevent them from becoming breeding sites for mosquitoes as vectors.

Lymphatic Intervention, the Frontline of Modern Lymphatic Medicine: Part I. History, Anatomy, Physiology, and Diagnostic Imaging of the Lymphatic System.

Recent advances in lymphatic imaging have provided novel insights into the lymphatic system. Interventional radiology has played a significant role in the development of lymphatic imaging techniques and modalities. Radiologists should be familiar with the basic physiology and anatomy of the lymphatic system to understand the imaging features of lymphatic disorders, which reflect their pathophysiology. This study comprehensively reviews the physiological and anatomical aspects of the human lymphatic system as well as the latest lymphatic imaging techniques.

History of the development of the lymphatic system (part two)

The eighteenth century can rightly be considered the time of the most remarkable inventions in studying the lymphatic system. The Swiss Johann Conrad Peyer (1653–1712), in his "Exercitatio anatomico-medica de glandulis intestinorum earumque usu et affectionibus" (1677) described the presence of organized lymphatic vessels in the mucous membrane of the small intestine, which are named Peyer's plaques in his honor. Alexander Monro from the University of Edinburgh Medical School was the first to describe the function of the lymphatic system in detail. In 1701, Dutch botanist and anatomist Frederick Ruysch (1638-1731), a student of Van Horn, described the morphology and function of lymphatic valves. Another Dutch anatomist, Anton Nyuck (1650-1692), used the mercury injection technique to demonstrate the lymphatic system. The French anatomist Raymond Vuyssens (1641-1715), a pioneer in cardiac and nervous system anatomy, published his groundbreaking work in Nouvelles Découvertes sur le Coeur (1706) detailing the lymphatic system of the heart. The Italian histologist and microscopist Marcello Malpighi (1628–1689) gave a great impetus to the development of microanatomy with his pioneering microscope. New progress in the knowledge of the lymphatic system was provided by the English Hunter brothers. William Hunter (1718-1783) clearly suggested that lymphatic and milk vessels have two different properties that contribute to the formation of a single network of vessels endowed with an absorbing function. In 1731, Antonio Leprotti published a dissertation on the roots of the human lymphatic system. The Italian anatomist Paolo Mascagni (1755-1815) developed a special instrument with glass tubes for slowly introducing mercury into the lymphatic vessels. In the same year, 1787, Paolo Assalini published an essay on the lymphatic system, where the author tried to demonstrate the existence of "air-conducting" vessels. Like Nyuck and Mascagna, Vincenzo Foman (1794-1837) used mercury to inject the smallest lymphatic vessels. Another contribution to understanding the anatomy of the lymphatic system made the French anatomist Marie Philibert Constant Sappey (1810-1896), who was able to count the valves in the lymphatic vessels. The Polish pathologist Alfred Besiadecki (1839-1889) made a great contribution to the study of the lymphatic system of the skin. Thanks to his research, he refuted the prevailing hypothesis that the blood capillaries in the skin are located inside the lymphatic vessels. For the first time in history, he described the contiguous connection between lymphatic and blood vessels. In 1858, Carl Friedrich Wilhelm Ludwig (1816-1895) proposed the hypothesis that lymph is a filtrate of blood that is released from the capillary wall under the influence of intracapillary pressure. After that, the British doctor William Handley significantly contributed to the development of surgery for lymphatic disorders. In 1908, he introduced his technique of "lymphangioplasty". One of the key figures of this lymphatic revolution and "renaissance" is undoubtedly the Finnish researcher Kari Kustaa Alitalo (1952-present), who, together with his group and in collaboration with other international groups, made the most important discoveries regarding the growth factor/receptor system that controls the development of lymphatic vessels and lymphatic metastases of tumors.

Hubungan Pengetahuan dan Sikap dengan Perilaku Pencegahan Filariasis di Kecamatan Cilimus Kabupaten Kuningan

Lymphatic filariasis is a chronic infectious disease caused by parasitic nematodes. The worm can damage the human lymphatic system gradually then causing enlargement of the limbs, breasts and genitalia. Kuningan is an endemic regency for filariasis in West Java Province. Cilimus District was in the 2nd position as a district with the highest filariasis cases in Kuningan in 2017. This research was conducted in Cilimus District from May to June 2018 using a cross-sectional design. The population was all households in the Cilimus District with a sample size of 106 people who were taken using a simple random sampling technique. The independent variables studied were knowledge and attitudes regarding the prevention of filariasis, the dependent variable was the filariasis prevention practices. Data collection was carried out by interview using a questionnaire. Data analysis was performed by univariate and bivariate (chi-square test). The results showed that some respondents had good knowledge and positive attitudes about the prevention of filariasis (50%). The description of respondent practices showed that 82.1% of respondents took filariasis drug, 62.3% of respondents had the habit of using mosquito repellent, only 4.7% of respondents used mosquito nets, 49.1% of respondents put gauze wire, 47.2% of respondents did not have a habit of hanging clothes. The results of categorizing behavioral variables were found that more than half of the respondents (52.8%) had implemented good prevention practices. The results of the bivariate analysis showed that there was a significant relationship between knowledge and attitude with filariasis prevention practices (p <0.05).

Graph Theory for Modeling and Analysis of the Human Lymphatic System

The human lymphatic system (HLS) is a complex network of lymphatic organs linked through the lymphatic vessels. We present a graph theory-based approach to model and analyze the human lymphatic network. Two different methods of building a graph are considered: the method using anatomical data directly and the method based on a system of rules derived from structural analysis of HLS. A simple anatomical data-based graph is converted to an oriented graph by quantifying the steady-state fluid balance in the lymphatic network with the use of the Poiseuille equation in vessels and the mass conservation at vessel junctions. A computational algorithm for the generation of the rule-based random graph is developed and implemented. Some fundamental characteristics of the two types of HLS graph models are analyzed using different metrics such as graph energy, clustering, robustness, etc.

Effective Single Drug Treatment of Lymphatic Filariasis through Enhanced Transdermal Delivery of Ivermectin Liposomes using Solid and Dissolving Microneedles

Abstract: Objectives: The present investigation was to study the combination of liposomes (LP) and microneedles (MNs) as a single drug treatment approach for the delivery of an antifilarial drug, ivermectin (IVM) in which the role of MN arrays (commercial solid MNs of different lengths and laboratory fabricated polymeric dissolving MNs of length 0.6mm) in increasing the in vitro permeation of IVM-LP across pig ear skin was studied. Experimental: IVMLP was formulated and optimized using solvent injection method and thin layer film hydration method. The optimized IVM-LP formulation F4 were then incorporated into the dissolving MN arrays and tested for the increased permeation of IVM by the assistance of MNs. A transdermal patch with IVM-LP was prepared as passive permeation study. Solid MNs (poke and patch) were tested for assisting the penetration of IVM from IVMLP patch. In vitro skin permeation studies were carried out using Franz diffusion cells for a period of 24 h. Results and Discussion: The optimized IVM-LP was < 100 nm in diameter suitable for lymphatic uptake and MNs of IVM-LP had good mechanical strength, insertion capabilities. From the dermatokinetic study it was evident that the delivery of IVM into the excised porcine skin by MNs was significantly higher than that from passive studies, with apparent permeability coefficient of 0.798±0.009 cm/h for 0.6mm dissolving MNs. Conclusion: MN assisted transdermal delivery of IVM-LP could be used to target specifically human lymphatic system where single drug treatment for lymphatic filariasis could be made possible. Key words: Lymphatic filariasis, Ivermectin, Liposomes, Microneedles, Transdermal drug delivery systems, Bioavailability.

Simulation of lymph flow with consideration of natural gravity force influence

The model of lymph flow in the human lymphatic system in the quasi-one-dimensional approach is considered in the paper. Calculations with natural gravity force influence are presented. Calculations show that in some sets of parameters of lymphatic vessels the physiological flow can be reached in the model with zero global pressure gradient influence only by the “muscle” pump.

Pump eflciency of lymphatic vessels: numeric estimation

Abstract A model of lymph flow in the human lymphatic system in the quasi-one-dimensional approach has been created and investigated under different conditions. The model includes an implementation of contractions and valve influence on lymph flow. We consider contractions of lymphatic vessels and their influence on resulting flow in the whole network of lymphatic vessels and lymph nodes. We have investigated flow with zero pressure gradient and have found parameters, which influence the efficiency of contractions most significantly.

Identification of anti-filarial leads against aspartate semialdehyde dehydrogenase of Wolbachia endosymbiont of Brugia malayi: combined molecular docking and molecular dynamics approaches

Lymphatic filariasis is a debilitating vector borne parasitic disease that infects human lymphatic system by nematode Brugia malayi. Currently available anti-filarial drugs are effective only on the larval stages of parasite. So far, no effective drugs are available for humans to treat filarial infections. In this regard, aspartate semialdehyde dehydrogenase (ASDase) in lysine biosynthetic pathway from Wolbachia endosymbiont Brugia malayi represents an attractive therapeutic target for the development of novel anti-filarial agents. In this present study, molecular modeling combined with molecular dynamics simulations and structure-based virtual screening were performed to identify potent lead molecules against ASDase. Based on Glide score, toxicity profile, binding affinity and mode of interactions with the ASDase, five potent lead molecules were selected. The molecular docking and dynamics results revealed that the amino acid residues Arg103, Asn133, Cys134, Gln161, Ser164, Lys218, Arg239, His246, and Asn321 plays a crucial role in effective binding of Top leads into the active site of ASDase. The stability of the ASDase-lead complexes was confirmed by running the 30 ns molecular dynamics simulations. The pharmacokinetic properties of the identified lead molecules are in the acceptable range. Furthermore, density functional theory and binding free energy calculations were performed to rank the lead molecules. Thus, the identified lead molecules can be used for the development of anti-filarial agents to combat the pathogenecity of Brugia malayi.

Developing Computational Geometry and Network Graph Models of Human Lymphatic System

The lymphatic system is a body-wide network of lymphatic vessels and lymphoid organs. The complexity of the structural and functional organization of the lymphatic system implies the necessity of using computational modeling approaches to unravel the mechanisms of its regulation in quantitative terms. Although it is a vital part of the circulatory and immune systems, the lymphatic system remains poorly investigated as a mathematical modeling object. Modeling of the lymphatic vessel network needs to be established using a systematic approach in order to advance the model-driven research of this important physiological system. In our study, we elucidate key general features underlying the 3D structural organization of the lymphatic system in order to develop computational geometry and network graph models of the human lymphatic system based on available anatomical data (from the PlasticBoy project), which provides an estimate of the structure of the lymphatic system, and to analyze the topological properties of the resulting models.

Utilizing lymphatic cell markers to visualize human lymphatic abnormalities.

In vivo visualization of the human lymphatic system is limited by the mode of delivery of tracing agents, depth of field and size of the area examined, and specificity of the cell markers used to distinguish lymphatic endothelium from the blood vessels and the surrounding tissues. These limitations are particularly problematic when imaging human lymphatic abnormalities. First, limited understanding of the lymphatic disease aetiology exists with respect to genetic causes and phenotypic presentations. Second, the ability of a tracer to reach the entire lymphatic network within the diseased tissue is suboptimal. Third, what is known about the expression of lymphatic endothelial cell (LEC) markers, such as podoplanin, lymphatic vessel endothelial hyaluronan receptor, Drosophila melanogaster homeobox gene prospero-1 and vascular endothelial growth factor receptor-3 in rodent lymphatic vessels and healthy human LECs may not necessarily apply in human lymphatic disease settings. The aim of this review is to highlight challenges in visualizing lymphatic vessels in human lymphatic abnormalities with respect to distribution patterns of the cellular markers currently employed to visualize abnormal human lymphatic vessels in experimental settings. Allowing for these limitations within new diagnostic visualization technologies is likely to improve our ability to image human lymphatic diseases.

Imaging lymphatics in human normal and lymphedema limbs-Usefulness of various modalities for evaluation of lymph and edema fluid flow pathways and dynamics.

The human lymphatic system morphology and function still remain largely unknown to clinicians and biologists. How does the lymphatic vascular system look like in comparison to the blood transport system, how does lymph flow, where does capillary filtrate accumulate in cases with lymphatic obstruction caused by inflammation, trauma, and cancer therapy, remain as basic questions. Visualization of the lymphatic pathways and dynamics of lymph flow, and in cases of obstruction, the localization of the capillary filtrate/edema fluid accumulation becomes indispensable. The contemporary methods only partly meet these requirements. Since the early 1950s of the 20th century only few specific clinical methods of imaging of limb lymphatics are being used in human clinic. Each of the applied modalities provides different images due to different physical chemistry and distribution of tracer, methods used for its detection in tissues, their sensitivity and specificity and clinical type of lymph vessel pathology. Here, the advantages and disadvantages of the most commonly used 3 methods of imaging: the iodinated oil X-ray, isotopic, and fluorescent lympangiographies are presented. The study is based on retrospective and recent collections of lymphangiograms from large cohorts of patients. Imaging of lymph nodes has not been included as it is requiring different interpretation compared with vessels. Composite evaluation of X-ray, isotopic, and fluorescent lymphographic images or, as it is practiced now the isotope and indocyanine green near infrared lymphographies, provide most clinically important information. Special attention was directed at methods enabling early diagnosis of imminent lymphedema especially in cases with cancer therapy-related lymphedema. Groups of typical images obtained with the 3 methods are presented.

MicroRNA-520a attenuates proliferation of Raji cells through inhibition of AKT1/NF-κB and PERK/eIF2α signaling pathway.

Burkitt's lymphoma(BL) is a fast growing cancer of the human lymphatic system, and an extremely invasive B-cell non-Hodgkin's lymphoma. We explored the mechanism of apoptosis in Raji cells associated with the post-transcriptional regulation factors. To confirm that the predicted microRNA-520a(miR-520a) is matched with AKT1, 3'untranslated region(UTR) luciferase activity of AKT1 was used in the assessment. In the presence of the mimics or inhibitors of miR-520a, cell function of Raji, such as proliferation, growth and apoptosis were analyzed. The expression of endoplasmic reticulum(ER) stress‑related proteins were examined. Luciferase reporter analysis showed that miR‑520a leads to decreased activity of luciferase gene fused with AKT1 3'UTR. Therefore, AKT1 is a direct target of miR‑520a. Our data indicated that the mimics of miR‑520a inhibited growth, proliferation of Raji cells and promoted its apoptosis, which was related to downregulation of AKT1, NF‑κB and ER stress response mediated by PERK/eIF2α pathway. On the contrary, the inhibitors of miR‑520a promoted growth, proliferation of Raji cells and inhibited its apoptosis, which was related to AKT1/NF‑κB and PERK/eIF2α pathway. We identified miR‑520a, which specifically binds to AKT1 mRNA 3'UTR. miR‑520a is a crucial mediator for proliferation and ER stress in Raji cells through regulating the AKT1/NF‑κB or PERK/eIF2α signaling pathway. Our findings suggest that targeting miR‑520a is a promising therapeutic strategy in BL.

An integrated in vitro imaging platform for characterizing filarial parasite behavior within a multicellular microenvironment.

Lymphatic Filariasis, a Neglected Tropical Disease, is caused by thread-like parasitic worms, including B. malayi, which migrate to the human lymphatic system following transmission. The parasites reside in collecting lymphatic vessels and lymph nodes for years, often resulting in lymphedema, elephantiasis or hydrocele. The mechanisms driving worm migration and retention within the lymphatics are currently unknown. We have developed an integrated in vitro imaging platform capable of quantifying B. malayi migration and behavior in a multicellular microenvironment relevant to the initial site of worm injection by incorporating the worm in a Polydimethylsiloxane (PDMS) microchannel in the presence of human dermal lymphatic endothelial cells (LECs) and human dermal fibroblasts (HDFs). The platform utilizes a motorized controllable microscope with CO2 and temperature regulation to allow for worm tracking experiments with high resolution over large length and time scales. Using post-acquisition algorithms, we quantified four parameters: 1) speed, 2) thrashing intensity, 3) percentage of time spent in a given cell region and 4) persistence ratio. We demonstrated the utility of our system by quantifying these parameters for L3 B. malayi in the presence of LECs and HDFs. Speed and thrashing increased in the presence of both cell types and were altered within minutes upon exposure to the anthelmintic drug, tetramisole. The worms displayed no targeted migration towards either cell type for the time course of this study (3 hours). When cells were not present in the chamber, worm thrashing correlated directly with worm speed. However, this correlation was lost in the presence of cells. The described platform provides the ability to further study B. malayi migration and behavior.

Johann Vesling (1598-1649): seventeenth century anatomist of Padua and his Syntagma Anatomicum.

Johann Vesling (1598-1649) was a German anatomist and surgeon who belonged to the golden period of the illustrious University of Padua. He made significant contributions to the advancement of anatomical knowledge during the 17th century and is remembered most for his remarkable anatomical work, the Syntagma Anatomicum, which was published in 1641. He was the first to describe the soleus muscle and to emphasize its resemblance to the sole fish. He produced the earliest illustrations of the human lymphatic system and was one of the first to document observations about the thoracic duct. He was also the first to report the bifurcation of the human hepatic portal vein on entering the fissure of the liver. His observations from embryological experiments were critical for understanding the development of the four-chambered heart. He was one of the first authors to state that four pulmonary veins empty into the left atrium of the heart. Syntagma Anatomicum (1641) was the most widely used anatomical text in Europe for almost a century and was republished a number of times with editions in Latin, German, Dutch, and English. Syntagma was the first illustrated western anatomical text to reach Japan and laid the foundation for the development of European medicine there. The illustrations used in it deviated from the artistic convention that had characterized anatomical figures from the time of Vesalius, and focused instead on representing anatomical details to make them helpful for medicine and surgery. Clin. Anat. 27:1122-1127, 2014. © 2014 Wiley Periodicals, Inc.

Improved antifilarial activity of ivermectin in chitosan–alginate nanoparticles against human lymphatic filarial parasite, Brugia malayi

The current antifilarial treatments are not up to the mark partly due to deep location of filarial parasites in the human lymphatic system. We report here on the improvement in the antifilarial activity of ivermectin (IVM) using chitosan-alginate nanoparticles prepared by modified complex coacervation method. The nanoparticles were spherical having 155 nm size and 4.56 and 75.67% loading and entrapment efficiency respectively for IVM. The delivery system maintained the sustained release and significantly augmented the microfilaricidal (MIF) activity at a single low dose (200 μg/kg body weight, subcutaneously) in contrast to much higher dose of free ivermectin (400 μg/kg body weight, subcutaneously) against human lymphatic filariid, Brugia malayi in rodent host, Mastomys coucha. To substantiate increase in MIF activity, pharmacokinetics study was designed on Wistar rats which revealed a greater peak plasma concentration (45.3 ± 1.79 ng/ml), area under the concentration curve (298 ± 38.7 ng d/ml) and extended mean residence time (23.4 ± 8.56 days)of IVM in chitosan-alginate nanoparticles. Administration of 25 mg/kg of diethylcarbamazine following nanoparticle therapy significantly improved the MIF and macrofilaricidal action of encapsulated drug and was considered superior in this study.

Synthesis and Macrofilaricidal Activity of Substituted 2‐Hydroxy/5‐Hydroxy/2‐Methyl‐1,4‐Naphthoquinones

Abstract Preclinical Research Lymphatic filariasis is a disfiguring disease caused by parasitic worms that destroy the human lymphatic system leading to substantial morbidity. The current drug of choice for the treatment of filariasis is diethylcarbamazine and ivermectin with albendazole which are only effective against the microfilaria, leaving the adult worm unaffected, requiring the development of “adulticidal drugs.” Thirty amino substituted 2‐hydroxy/5‐hydroxy/2‐methyl‐1,4‐naphthoquinones were synthesized via the reaction of 2‐hydroxy/5‐hydroxy/2‐methyl‐1,4‐naphthoquinones with different primary and secondary amines. Compounds 1–30 were evaluated for in vitro antifilarial activity against the adult bovine filarial worm Setaria digitata as assessed by worm motility and MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) reduction assays. The mutagenecity, tumerogenecity, irritantancy, reproductive toxicity, drug score, druglike, and cLogP properties were calculated using OSIRIS property predictor. Ten compounds showed macrofilaricidal activity with ED50 values ranging between 0.086 and 7.6 μM. Taking into account the biological effects and the promising drug‐like profiles of these compounds, these represent valid leads for the development of antifilarial agents against adult filarial worm.

Association of CTLA4 gene polymorphisms with lymphatic filariasis in an East Malaysian population

Lymphatic filariasis (LF) is a parasitic disease caused by threadlike worms of the Brugia and Wuchereria species that live in the human lymphatic system. Regulatory T cells (Tregs) may play a key role in the pathogenesis of LF, and cytotoxic T-lymphocyte antigen-4 (CTLA4) expressed by Tregs is a potential candidate gene because it modulates T-cell activation. A case–control study was performed to establish a potential association of 5 CTLA4 gene promoter single nucleotide polymorphisms (SNPs; rs733618, rs11571316, rs5742909, rs231775, and rs16840252) with the occurrence of LF in an East Malaysian population (320 LF-infected individuals and 150 healthy controls). Polymorphisms were evaluated using TaqMan real-time polymerase chain reaction followed by direct sequencing. LF carriers of the rs733618 AG genotypes ( p = 0.02) and those with combined minor allele G carriers (AG + GG; p = 0.01) exhibited a significantly decreased risk for LF. Among the asymptomatic amicrofilaremic cases, positive associations were reported for all genotypes and variants of rs733618 with odds ratios (ORs) ranging from 0.27 to 0.45. In the asymptomatic microfilaremic cases, marker rs231775 exhibited a significant decreased risk, with ORs ranging from 0.50 to 0.57. The study has identified SNPs in the CTLA4 promoter gene that may be functionally linked with susceptibility to LF.