Biocompatible gelatin-coated ferrite nanoparticles: A magnetic approach to advanced drug delivery.

Nanotechnology has transformed drug delivery, offering opportunities to enhance treatment outcomes while minimizing adverse effects. This study focuses on gelatin-coated cobalt and manganese ferrite nanoparticles for potential drug delivery applications. The synthesis involved a co-precipitation method, and the nanoparticles were characterized using various techniques, including X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, and vibrating sample magnetometer (VSM). Results revealed stable structures, distinct chemical features introduced by gelatin coating, and unique magnetic properties. The hemolysis assay demonstrated reduced hemolytic activity with gelatin coating, enhancing biocompatibility. Drug release studies indicated differential release profiles, with gelatin-coated cobalt ferrite exhibiting higher drug release compared to gelatin-coated manganese ferrite. The Higuchi model supported diffusion-controlled drug release for gelatin-coated cobalt ferrite. These findings suggest the potential of gelatin-coated ferrite nanoparticles for controlled and targeted drug delivery, highlighting their significance in advancing nanomedicine.

In silico analysis of non-synonymous missense SNPs (nsSNPs) in CPE, GNAS genes and experimental validation in type II diabetes mellitus through Next Generation Sequencing.

Non-synonymous missense SNPs (nsSNPs) in CPE and GNAS genes were investigated computationally. In silico identified nsSNPs were experimentally validated in type II diabetes mellitus (T2DM) in Pakistani Pathan population using next generation sequencing (NGS). Sixty two high-risk nsSNPs in CPE and 44 in GNAS were identified. Only 12 in GNAS were clinically significant. Thirty six high-risk nsSNPs in CPE and 08 clinically significant nsSNPs in GNAS lies in the most conserved regions. I-mutant predicted that nsSNPs decrease the proteins stability and ModPred predicted 20 and 12 post-translational modification sites in CPE and GNAS proteins respectively. Ramachandran plot showed 88.7% residues are in the most favored region of protein models. By experimentation, none of the nsSNPs were found to be associated with T2DM. In conclusion, this study differentiates the deleterious nsSNPs from the neutral ones. Although nsSNPs are not associated with T2DM, they can be targeted in other CPE and GNAS genes related disorders.

The prognostic outcome of 'type 2 diabetes mellitus and breast cancer' association pivots on hypoxia-hyperglycemia axis.

Type 2 diabetes mellitus and breast cancer are complex, chronic, heterogeneous, and multi-factorial diseases; with common risk factors including but not limited to diet, obesity, and age. They also share mutually inclusive phenotypic features such as the metabolic deregulations resulting from hyperglycemia, hypoxic conditions and hormonal imbalances. Although, the association between diabetes and cancer has long been speculated; however, the exact molecular nature of this link remains to be fully elucidated. Both the diseases are leading causes of death worldwide and a causal relationship between the two if not addressed, may translate into a major global health concern. Previous studies have hypothesized hyperglycemia, hyperinsulinemia, hormonal imbalances and chronic inflammation, as some of the possible grounds for explaining how diabetes may lead to cancer initiation, yet further research still needs to be done to validate these proposed mechanisms. At the crux of this dilemma, hyperglycemia and hypoxia are two intimately related states involving an intricate level of crosstalk and hypoxia inducible factor 1, at the center of this, plays a key role in mediating an aggressive disease state, particularly in solid tumors such as breast cancer. Subsequently, elucidating the role of HIF1 in establishing the diabetes-breast cancer link on hypoxia-hyperglycemia axis may not only provide an insight into the molecular mechanisms underlying the association but also, illuminate on the prognostic outcome of the therapeutic targeting of HIF1 signaling in diabetic patients with breast cancer or vice versa. Hence, this review highlights the critical role of HIF1 signaling in patients with both T2DM and breast cancer, potentiates its significance as a prognostic marker in comorbid patients, and further discusses the potential prognostic outcome of targeting HIF1, subsequently establishing the pressing need for HIF1 molecular profiling-based patient selection leading to more effective therapeutic strategies emerging from personalized medicine.

Impact of HPV E5 on viral life cycle via EGFR signaling.

Oncoprotein E5 is gaining popularity with time as the third transforming protein of Human Papillomavirus (HPV). Extensive proliferation is the distinguished feature of developing cancers, and E5 is able to stimulate keratinocytes proliferation via upregulation of EGFR signaling pathway. Thus E5 is thought to indirectly contribute to the completion of the viral life-cycle by generating the adequate cellular environment. By amplifying EGFR signaling E5 delays differentiation and allows hyperproliferation of keratinocytes which otherwise would have followed a normal differentiation pathway. Thus exploring the mechanisms by which HPV E5 regulates signaling by EGFR receptors in detail suggest new ways of inhibiting HPV-mediated disease progression.

Nanomedicine: an emerging era of theranostics and therapeutics for rheumatoid arthritis.

RA is a multifactorial autoimmune inflammatory disease characterized by synovitis, bone destruction and joint dysfunction that leads to shortening of lifespan and increased mortality rates. Currently available treatments of RA, by controlling various symptoms, only delay disease progression and have their own side effects. Consequently, there is the need for a novel therapeutic strategy that offers a more sustainable and biocompatible solution. Nanomedicine is a modern branch of nanobiotechnology that provides targeted therapy to inflamed rheumatic joints and thus prevents unwanted off-target side effects. This review highlights various nanotheranostic and nanotherapeutic strategies that are currently being used for the treatment of RA.

T cell activation Rho GTPase activating protein (TAGAP) is upregulated in clinical and experimental arthritis.

Genome-wide association studies have identified various susceptibility variants and loci associated with incidence of rheumatoid arthritis (RA) in different populations. One of these is T cell activation Rho GTPase activating protein (TAGAP). The present study sought to measure the expression of TAGAP in RA patients, CD4+ T cells subsets from healthy humans and in mice with collagen-induced arthritis. Peripheral blood mononuclear cells (PBMC) from RA patients and tissues of arthritic mice at different stages of the disease were used for the evaluation of TAGAP mRNA expression. Increased TAGAP expression was observed in RA patients compared to healthy controls, and there were differences in the expression level of TAGAP in the tissues of mice with experimental arthritis. Gene expression in CD4+ T cells from healthy humans was greatest 4 h after activation and protein expression was greatest after 24 h. The expression of TAGAP was not correlated with CD4+ lymphocyte subsets which were enriched for functionally defined subsets (Th17, Treg, Th1), further indicating its utility as an indicator of lymphocyte activation. These findings indicate that increased TAGAP expression is a distinguishing feature of inflammatory disease and further highlight the role of TAGAP in RA susceptibility.

Immunomodulatory and therapeutic role of Cinnamomum verum extracts in collagen-induced arthritic BALB/c mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum verum (CV), also known as 'Dalchini', is the dry bark of the Cinnamomum verum (L.) plant, and has been used as a traditional Pakistani medicine to alleviate pain and inflammation in patients suffering from arthritic rheumatism. It contains alkaloids, triterpenes, Cinnamaldehyde and other volatile oils. The aim of the present study was to investigate the underlying biological effect of ethyl alcohol (EtOH) and methyl alcohol (MeOH) extracts from CV on collagen type-II induced arthritic (CIA) mice. MATERIALS AND METHODS: Gas chromatography mass spectrophotometry was used to perform fingerprinting identification of the EtOH and MeOH extracts. CIA mice model was established by subdermal injections of type-II bovine collagen (CII) on the 1st, 8th and 14th day of the experiment. Ethyl alcohol extract and methyl alcohol extract (1 mg/KgBW, 2 mg/KgBW and 4 mg/KgBW), was orally administered from the 15th day onwards for 2 weeks. Progression of oedema and joint inflammation was measured in the paws using a digital Vernier calliper every 3 days from day 1 till the end of the experiment. The oxidative scavenging ability of cinnamaldehyde was evaluated using a DPPH assay. Similarly, the nitrogen free radical (NOS) production of isolated lymphocytes was evaluated using Greiss's method. The spleen index was calculated and knee joint changes were observed by histopathological sectioning. Western blot analysis was performed on peripheral blood derived serum for CII, CAPN1, TNFα and NFATc3. RESULTS: Extracts were shown to be enriched in trans-cinnamaldehyde and its analogues. Extracts showed good ameliorative effects (p < 0.05) after day 2 of treatment. A greater therapeutic role was observed for the 4 mg/kgBW dosage of the methanolic extract (p < 0.01). Swelling in the spleen was greatly reduced along with the generation of free radicals by lymphocytes, post treatment. There was also an inhibitory role by the extracts on NFATc3 (p < 0.05), TNF-Alpha (p < 0.05), CAII (p < 0.05) and mCalpain (p < 0.05) all proteins involved in RA. CONCLUSION: In this study, it has been demonstrated that administration of CV has a therapeutic potential on CIA. The data suggest that CV could have a potential role in the treatment of RA patients.

Mutations in DCPS and EDC3 in autosomal recessive intellectual disability indicate a crucial role for mRNA decapping in neurodevelopment.

There are two known mRNA degradation pathways, 3' to 5' and 5' to 3'. We identified likely pathogenic variants in two genes involved in these two pathways in individuals with intellectual disability. In a large family with multiple branches, we identified biallelic variants in DCPS in three affected individuals; a splice site variant (c.636+1G>A) that results in an in-frame insertion of 45 nucleotides and a missense variant (c.947C>T; p.Thr316Met). DCPS decaps the cap structure generated by 3' to 5' exonucleolytic degradation of mRNA. In vitro decapping assays showed an ablation of decapping function for both variants in DCPS. In another family, we identified a homozygous mutation (c.161T>C; p.Phe54Ser) in EDC3 in two affected children. EDC3 stimulates DCP2, which decaps mRNAs at the beginning of the 5' to 3' degradation pathway. In vitro decapping assays showed that altered EDC3 is unable to enhance DCP2 decapping at low concentrations and even inhibits DCP2 decapping at high concentration. We show that individuals with biallelic mutations in these genes of seemingly central functions are viable and that these possibly lead to impairment of neurological functions linking mRNA decapping to normal cognition. Our results further affirm an emerging theme linking aberrant mRNA metabolism to neurological defects.

Progression pattern of rheumatoid arthritis: A study of 500 Pakistani patients.

To estimate the most prevalent age of patients and disease status and progression in terms of severity at different age groups in the Pakistani Rheumatoid Arthritis (RA) patients. A total of five hundred (500) RA patients were enrolled during October, 2009 to October, 2013. A screening questionnaire was filled for each patient satisfying America College of Rheumatology (ACR) criteria under the supervision of certified rheumatologists. Epidemiological and demographic variables were statistically analyzed for correlation with progression of the disease using SPSS ver 17.0.1 software. In general, rheumatoid arthritis preferentially affects women with female to male ratio of about 3:1; however, patients with above 60 years of age have equal female to male ratio. The most prevalent age is 45-60 years. The disease severity increases with increase in the age and reaches to its peak in above 60 years of age (p=0.001). The pattern of progression of RA in the Pakistani patients is almost consistent with other relevant studies conducted on European and European derived populations.

The microRNA regulatory network: a far-reaching approach to the regulate the Wnt signaling pathway in number of diseases.

Wnt signaling pathway plays an important role in cell renewal, tumorigenesis, organogenesis, bone formation and bone resorption. Wnt signaling pathway is divided into two outlets: Wnt-ß-catenin pathway (canonical pathway) and Wnt-calcium pathway (non-canonical pathway). miRNAs play a key role in the regulation of Wnt signaling pathway. In this review, we highlight the basic indulgent of miRNAs-mediated regulation of Wnt signaling pathway. We focus on the role of miRNAs at different levels of Wnt signaling: signaling molecules, their associated signaling proteins, regulatory proteins, transcription factors and related cytokines. Finally, we concluded that these multiple levels of targeting may have diagnostic potential as well as therapeutic prospective in future treatment.

Polymorphisms in DNA repair genes XRCC1 and OGG1 lead to the progression of rheumatoid arthritis in Pakistani patients.

This study points at the elucidation of a possible association of Rheumatoid arthritis (RA) with Ser326Cys in OGG1 Arg194Trp and Arg399Gln polymorphisms of XRCC1 using a sample size of 100 patients and 100 controls from a Pakistani population. This association was determined using Random Fragment Length Polymorphism Analysis as well as the DAS scoring system. In RA, oxidative damage due to free radical production leads to destructive proliferative synovitis showing cellular transformations of synoviocytes into a tumorigenic state. XRCC1 and OGG1 genes, which are part of the DNA Break Excision Repair pathway, manifest various polymorphisms which may cause a variation in the response to inflammation by changing DNA repair potential. Our results showed a significant association between the DAS28 score values as well as the genotypic state of the RA patients. It was seen that the score was significantly higher in GG genotypes thereby corroborating the role of the polymorphism XRCC1 Arg399Gln. Using a Pearson's correlation test it was found to be <0.000003. It has been shown by the results in this research that an increased risk of DNA damage exists when the polymorphic genotypes studied, exist in a RA patient.

Rheumatoid arthritis: What have we learned about the causing factors?

Rheumatoid Arthritis (RA) is a common inflammatory autoimmune disease characterized by the synovitis of both small and large joints, which may lead to the destruction of cartilage and bones causing significant disabilities due to erosion of bones surfaces, if left untreated. It is a multifactorial and heterogeneous disease having contribution of both genetic (50-60%) and environmental factors. The unawareness of general public might be a contributing factor in the high prevalence rate of RA world-wide. This review article focuses on the causing factors (genetics and environmental) involved in this devastating disease. We also gave brief overview of the treatment options and animal models of RA. The literature was reviewed using mesh terms in PubMed search ''etiology of RA, genetics of RA, environmental factors in RA, Genome Wide Association Studies (GWAS) in RA''. The data was thoroughly reviewed and comprehensive information was extracted to help the readers in improving understanding towards the mechanisms, which trigger the outcomes of RA. The more we increase awareness about RA, the better we manage this disease and hence can improve life style and socio-economic status.

In silico analysis of SIGMAR1 variant (rs4879809) segregating in a consanguineous Pakistani family showing amyotrophic lateral sclerosis without frontotemporal lobar dementia.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. It has been found to be associated with frontotemporal lobar degeneration (FTLD). In the present study, we have described homozygosity mapping and gene sequencing in a consanguineous autosomal recessive Pakistani family showing non-juvenile ALS without signs of FTLD. Gene mapping was carried out in all recruited family members using microsatellite markers, and linkage was established with sigma non-opioid intracellular receptor 1 (SIGMAR1) gene at chromosome 9p13.2. Gene sequencing of SIGMAR1 revealed a novel 3'-UTR nucleotide variation c.672*31A>G (rs4879809) segregating with disease in this family. The C9ORF72 repeat region in intron 1, previously implicated in a related phenotype, was excluded through linkage, and further confirmation of exclusion was obtained by amplifying intron 1 of C9ORF72 with multiple primers in affected individuals and controls. In silico analysis was carried out to explore the possible role of 3'-UTR variant of SIGMAR1 in ALS. The Regulatory RNA motif and Element Finder program revealed disturbance in miRNA (hsa-miR-1205) binding site due to this variation. ESEFinder analysis showed new SRSF1 and SRSF1-IgM-BRCA1 binding sites with significant scores due to this variation. Our results indicate that the 3'-UTR SIGMAR1 variant c.672*31A>G may have a role in the pathogenesis of ALS in this family.

Genetic link of type 1 diabetes susceptibility loci with rheumatoid arthritis in Pakistani patients.

Rheumatoid arthritis (RA) and type 1 diabetes (T1D) are two autoimmune disorders that have been reported to co-occur in the same subjects or in different subjects from the same family. This suggests the sharing of disease susceptibility loci between RA and T1D. This study was aimed to find out such susceptibility loci that are common in both T1D and RA in Pakistani population. A total of 366 Pakistanis comprising related and unrelated RA cases and controls were recruited. Blood samples were collected from all patients followed by DNA isolation. Thirty-one single-nucleotide polymorphisms (SNPs) previously reported to be associated with T1D were genotyped in RA cases and controls using TaqMan SNP genotyping assays. Data was analyzed using FamCC software. We have identified seven SNP associations that survived multiple testing corrections using false discovery rate: SKAP2/rs7804356 (p = 2.47E-04), GLIS3/rs7020673 (p = 2.86E-04), GSDMB/rs2290400 (p = 23.48E-04), BACH2/rs11755527 (p = 9.16E-04), C6orf173/ rs9388489 (p = 3.11E-03), PRKCQ/DKFZp667F0711/ rs947474 (p = 4.53E-03), and DLK1/ rs941576 (p = 9.51E-03). Our results support the presence of overlapping loci between RA and T1D in Pakistani patients.

Homozygosity mapping of autosomal recessive intellectual disability loci in 11 consanguineous Pakistani families.

BACKGROUND: Autosomal recessive intellectual disability (ID) is genetically heterogeneous and most of the genes causing it remain undiscovered. OBJECTIVE: We have ascertained 11 consanguineous families multiplex for IDs in order to identify new loci for autosomal recessive genes for non-syndromic ID, or to aid pinpointing mutations in known causative gene/loci. Methodology Microarray genotyping (Affymatrix 250K) was performed to identify homozygosity-by-descent (HBD) in all affected families. RESULTS: Analysis of genotypes revealed 45 potential HBD regions across the families, although these may be rationalised down to 39. Two families share an overlapping HBD region on 7q11.21. In one family, X-linkage also looks plausible, and a new ID gene near the centromere may be a likely cause. In one family, no HBD region was found, and thus we exclude autosomal recessive mutation as the likely cause in this family. Copy-number variation (CNV) was also performed and revealed no CNVs, homozygous or heterozygous, segregating with the phenotype. CONCLUSION: The homozygous loci identified in this study might harbour candidate genes for ID in these studied families. Therefore, we are proceeding with next-generation sequencing analysis of the families, using whole-exome approaches, and anticipate that this will identify the causative gene/mutation within the identified HBD regions for many of the families studied here.

Identification of a homozygous splice site mutation in the dynein axonemal light chain 4 gene on 22q13.1 in a large consanguineous family from Pakistan with congenital mirror movement disorder.

Mirror movements (MRMV) are involuntary movements on one side of the body that mirror voluntary movements on the opposite side. Congenital mirror movement disorder is a rare, typically autosomal-dominant disorder, although it has been suspected that some sporadic cases may be due to recessive inheritance. Using a linkage analysis and a candidate gene approach, two genes have been implicated in congenital MRMV disorder to date: DCC on 18q21.2 (MRMV1), which encodes a netrin receptor, and RAD51 on 15q15.1 (MRMV2), which is involved in the maintenance of genomic integrity. Here, we describe a large consanguineous Pakistani family with 11 cases of congenital MRMV disorder reported across five generations, with autosomal recessive inheritance likely. Sanger sequencing of DCC and RAD51 did not identify a mutation. We then employed microarray genotyping and autozygosity mapping to identify a shared region of homozygosity-by-descent among the affected individuals. We identified a large autozygous region of ~3.3 Mb on chromosome 22q13.1 (Chr22:36605976-39904648). We used Sanger sequencing to exclude several candidate genes within this region, including DMC1 and NPTXR. Whole exome sequencing was employed, and identified a splice site mutation in the dynein axonemal light chain 4 gene, DNAL4. This splice site change leads to skipping of exon 3, and omission of 28 amino acids from DNAL4 protein. Linkage analysis using Simwalk2 gives a maximum Lod score of 6.197 at this locus. Whether or how DNAL4 function may relate to the function of DCC or RAD51 is not known. Also, there is no suggestion of primary ciliary dyskinesis, situs inversus, or defective sperm in affected family members, which might be anticipated given a putative role for DNAL4 in axonemal-based dynein complexes. We suggest that DNAL4 plays a role in the cytoplasmic dynein complex for netrin-1-directed retrograde transport, and in commissural neurons of the corpus callosum in particular. This, in turn, could lead to faulty cross-brain wiring, resulting in MRMV.

MicroRNAs with a role in gene regulation and in human diseases.

MicroRNAs (miRNAs) are short 20-22 nucleotide non-coding RNA sequences. Recently identified, these are novel regulators of gene expression at translational level as well as transcriptional level. Alteration in miRNAs level has been observed in a number of human diseases and studies have been conducted on the effect of altered expression level of miRNAs on the development and progression of different diseases. The miRNAs can be used as molecular biomarkers in a number of diseases. Also, miRNAs are promising in providing a new platform for molecular therapeutics of previously incurable diseases. This review will focus on the introduction, recent advances in the field of miRNA and its importance in some human disorders.

Association of Pro12Ala (rs1801282) variant of PPAR gamma with rheumatoid arthritis in a Pakistani population.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) belongs to a receptor superfamily of ligand-activated transcription factors, encoded by PPARG gene. Role of PPARγ has been well established in variety of metabolic disorders and in regulation of inflammation. In the present study, we aimed to investigate the association of PPARG (Pro12Ala; rs1801282) in clinically definite Pakistani Rheumatoid Arthritis (RA) patients and matching controls. The genotypes of the Pro12Ala variant in the PPARG were determined in a sample of 300 Pakistanis, including 150 RA cases and 150 controls. The genotyping was performed using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR) method, and the data was analyzed through Graphpad Prism 5 V software. Allele-specific primer set (two forward: PPARG-F1, PPARG-F2 and a common reverse primer: PPARG-R) was used for amplification, and the product was resolved on 2 % agarose gel. The CC (ProPro) genotype has higher frequency in controls than RA cases [75 (50.0 %) vs. 51 (34.0 %)], whereas the CG (ProAla) genotype has relatively same frequencies in both cases and controls [72 (48.0 %) vs. 70 (46.6 %)]. However, significantly higher frequency of GG (AlaAla) genotype was observed in cases [27 (18.0 %) vs. 5 (3.3 %); χ2 18.54; p < 0.0001]. Furthermore, the minor allele G has significantly higher allele frequency in cases having same trend and direction of association (OR 1.991(1.412-2.808); p < 0.0001). These observations suggest that Pro12Ala (rs1801282), a coding variant in the PPARG gene, is associated with Rheumatoid Arthritis in Pakistanis.

Transcriptomic Analysis of Alzheimer's Disease Pathways in a Pakistani Population.

Background: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that is most prevalent in elderly individuals, especially in developed countries, and its prevalence is now increasing in developing countries like Pakistan. Objective: Our goal was to characterize key genes and their levels of expression and related molecular transcriptome networks associated with AD pathogenesis in a pilot case-control study in a Pakistani population. Methods: To obtain the spectrum of molecular networks associated with pathogenesis in AD patients in Pakistan (comparing cases and controls), we used high-throughput qRT-PCR (TaqMan Low-Density Array; n = 33 subjects) coupled with Affymetrix Arrays (n = 8) and Ingenuity Pathway Analysis (IPA) to identify signature genes associated with Amyloid processing and disease pathways. Results: We confirmed 16 differentially expressed AD-related genes, including maximum fold changes observed in CAPNS2 and CAPN1. The global gene expression study observed that 61% and 39% of genes were significantly (p-value 0.05) up- and downregulated, respectively, in AD patients compared to healthy controls. The key pathways include, e.g., Amyloid Processing, Neuroinflammation Signaling, and ErbB4 Signaling. The top-scoring networks in Diseases and Disorders Development were Neurological Disease, Organismal Injury and Abnormalities, and Psychological Disorders. Conclusions: Our pilot study offers a non-invasive and efficient way of investigating gene expression patterns by combining TLDA and global gene expression method in AD patients by utilizing whole blood. This provides valuable insights into the expression status of genes related to Amyloid Processing, which could play potential role in future studies to identify sensitive, early biomarkers of AD in general.

Anti-citrullinated protein antibodies: role in pathogenesis of RA and potential as a diagnostic tool.

Rheumatoid arthritis is an autoimmune disorder which involves inflammation of the synovial tissue, leading to synovial proliferation, bone erosion and ultimately joint disability. It is a complex disorder, and the proper etiology is still unknown. Both environmental and genetic factors are responsible for the development of rheumatoid arthritis. Clinically, the disease is generally diagnosed by the presence of auto-antibodies like rheumatoid factor. But these are not specifically associated with rheumatoid arthritis. These are also present in patients with other autoimmune disorders and also in healthy persons. Citrullinated epitopes are shown to be more specific for rheumatoid arthritis. Citrullination normally occurs in cells undergoing apoptosis, and hence, citrullinated proteins are cleared from body and not encountered by immune system. However, in rheumatoid arthritis patients, these are not cleared. Anti-citrullinated protein antibodies are detectable in patients at risk of rheumatoid arthritis long before the onset of the disease. The concentration of which normally increases as the disease progress. Hence, these are important for diagnosis of rheumatoid arthritis. This review is focused on the importance of anti-citrullinated protein antibodies in disease pathogenesis and its importance in the diagnosis of rheumatoid arthritis.