CD4 Lymphopenia Research Articles

Disseminated nontuberculous mycobacterial infection in a patient with idiopathic CD4 lymphocytopenia and IFN-γ neutralizing antibodies: a case report

BackgroundDisseminated nontuberculous mycobacterial (NTM) infection usually occurs in immunodeficient patients, such as those with human immunodeficiency virus infection and idiopathic CD4 lymphopenia. However, disseminated NTM diseases have also been reported in immunocompetent patients. Autoantibodies to interferon-gamma (IFN-γ) are known to be involved in disseminated NTM disease, although anti-IFN-γ antibodies are mainly seen in immunocompetent patients rather than those with immunodeficiency. Here, we report a rare case of disseminated NTM patient with idiopathic CD4 lymphopenia and anti-IFN-γ antibodies.Case presentationA 64-year-old Asian male presented with fever, back pain, anorexia and weight loss. Physical examination revealed subcutaneous masses in the forehead, sternoclavicular joint, and right inguinal region. Computed tomography showed multiple osteosclerotic changes with soft structures and osteolytic changes. Both blood and sputum cultures were positive for Mycobacterium intracellulare, confirming the presence of disseminated NTM infection. Histopathological evaluation of the subcutaneous mass in the right inguinal region showed numerous granulomas consisting of epithelioid cells with Langhans-type giant cells. He was diagnosed with idiopathic CD4 lymphocytopenia. Interestingly, he also had anti-IFN-γ autoantibodies with suppression of IFN-γ-dependent signal transducer and activator of transcription 1 (STAT1) phosphorylation. Two-drug combination therapy with clarithromycin and ethambutol was started for the NTM infection, which resulted in a favorable disease course.ConclusionsIn patients with disseminated NTM infection, idiopathic CD4 lymphocytopenia and anti-IFN-γ autoantibody-positive immunodeficiency can be coexisted. It is necessary to clarify the pathogenesis and clinical course of CD4 lymphocytopenic conditions and IFN-γ neutralizing antibody-positive in the disseminated NTM disease.

Lymphocyte disturbance and functional assessment of the [Asp521Asn] ZAP70 mutation

Activated zeta-chain-associated protein kinase 70 (ZAP70) phosphorylates the TCRαβ:CD3:zeta complex to diversify and amplify TCR signaling. Patients with ZAP70 mutations can present with phenotypes of immune dysregulation as well as infection. We identified the first Taiwanese boy with the [Asp521Asn] ZAP70 mutation who presented with recurrent pneumonia, inflammatory bowel disease-like diarrhea, transient hematuria and autoimmune hepatitis. He had isolated CD8 lymphopenia, eosinophilia, hypogammaglobulinemia, and impaired lymphocyte proliferation. Downstream CD3/CD28 signaling, phosphorylation of AKT, ZAP70 and Ca2+ influx were decreased in [Asp521Asn] ZAP70 lymphocytes. Immunophenotyping analysis revealed expansion of transitional B and CD21-low B cells, Th2-skewing T follicular helper cells, but lower Treg cells. The Asp521Asn-ZAP70 hindered TCR-CD3 downstream phosphorylation and disturbed lymphocyte subgroup “profiles” leading to autoimmunity/autoinflammation. Further large-scale studies are warranted to clarify this lymphocyte disturbance. The prognosis significantly depends on hematopoietic stem cell transplantation, but not the genotype, the presence of opportunistic infections or immune dysregulation.

A case of extensive verrucosis in 45-year-old women and CD4 lymphopenia treated with electrodessication using general anesthesia and isoprinosine

The human papilloma virus (HPV) is a viral infection that has a broad variety of clinical manifestation. The clinical manifestation really depends on the type of HPV virus and the immunity status of the host, particularly the cell-mediated immunity. Extensive verrucosis is one of the significant clinical manifestation of a disseminated HPV infection that is related with a severe immunodeficiency status. Electrodessication or laser surgery is a method of treatment that could directly destroy the lesion in one time. We described a case of a 45 years-old woman with extensive verrucosis. The patient complained multiple warts lesion on the hands, face, neck, lower arms and lower extremities since eight years ago. Physical examination revealed on the dorsum and palmar hands, both of finger nails (I, II, III, and IV), face (forehead and cheeks), anterior of neck, lower arms and 2/3 distal of lower extremities part anterior, there were single and groups of flesh coloured papules and flesh coloured plaques, skin colour papules with flat topped, greyish papules and greyish plaques with verrucous surfaces and brownish crusts. The CD4 count of the patient was 91 cells/µL. Skin biopsy and histopathology examinations showed hyperkeratosis, papillomatosis, and acanthosis with vacuole cell (koilocytes). The patient was treated with electrodessication using general anaesthesia and isoprinosine 3x500 mg. The result after two weeks post-treatment showed that there were no new lesions appeared on post electro surgery site. This case highlights the importance of the treatment for the success of extensive verrucosis with CD4 lymphopenia.

Idiopathic CD4 lymphocytopenia manifesting as chronic non-resolving pneumonia.

Idiopathic CD4 lymphocytopenia manifesting as chronic non-resolving pneumonia.

Molluscum contagiosum in an HIV-negative adult with idiopathic CD4 lymphocytopenia easily missed by dermatologists: a case report

Molluscum contagiosum in an HIV-negative adult with idiopathic CD4 lymphocytopenia easily missed by dermatologists: a case report

CD4+ T Cell Regulatory Network Underlies the Decrease in Th1 and the Increase in Anergic and Th17 Subsets in Severe COVID-19.

In this model we use a dynamic and multistable Boolean regulatory network to provide a mechanistic explanation of the lymphopenia and dysregulation of CD4+ T cell subsets in COVID-19 and provide therapeutic targets. Using a previous model, the cytokine micro-environments found in mild, moderate, and severe COVID-19 with and without TGF-β and IL-10 was we simulated. It shows that as the severity of the disease increases, the number of antiviral Th1 cells decreases, while the the number of Th1-like regulatory and exhausted cells and the proportion between Th1 and Th1R cells increases. The addition of the regulatory cytokines TFG-β and IL-10 makes the Th1 attractor unstable and favors the Th17 and regulatory subsets. This is associated with the contradictory signals in the micro-environment that activate SOCS proteins that block the signaling pathways. Furthermore, it determined four possible therapeutic targets that increase the Th1 compartment in severe COVID-19: the activation of the IFN-γ pathway, or the inhibition of TGF-β or IL-10 pathways or SOCS1 protein; from these, inhibiting SOCS1 has the lowest number of predicted collateral effects. Finally, a tool is provided that allows simulations of specific cytokine environments and predictions of CD4 T cell subsets and possible interventions, as well as associated secondary effects.

Impact of CD4 T cells on intratumoral CD8 T-cell exhaustion and responsiveness to PD-1 blockade therapy in mouse brain tumors

BackgroundGlioblastoma is a fatal disease despite aggressive multimodal therapy. PD-1 blockade, a therapy that reinvigorates hypofunctional exhausted CD8 T cells (Tex) in many malignancies, has not shown efficacy in glioblastoma....

Opportunities for correction of immunosuppression in patients with COVID-19

Here, we review thematic publications in available literature sources of the databases PubMed, Scopus, Web of Science, eLibrary, 49 of which were dated of the years 19972022. Analysis of such reports is aimed at assessing features of cytokine storm-induced hyperinflammatory reaction with signs of immunosuppression accompanied by pronounced lymphopenia and lowered count of CD4+T helpers during severe COVID-19. The prognostic factor for unfavorable prognosis was based on the marker of systemic inflammatory reaction correlating with the disease severity the soluble IL-2 receptor as well as the neutrophil-to-lymphocyte ratio and the lymphocyte subset imbalance. An immunosuppressive therapy of severe forms of COVID-19, aimed at weakening the inflammatory response, exacerbates immune dysfunction by suppressing the T cell function, mainly due to Th1 lymphocytes involved in recognizing and eliminating intracellular pathogens particularly viruses. Upon that, cell-mediated immunity becomes compromised that relies on cytotoxic T-lymphocytes, natural killer cells and macrophages. Timely and targeted immunocorrection is required to prevent or reduce the immunosuppression that accompanies a severe disease course and leads to serious and prolonged complications, as well as to association of secondary infections. In fight against the cytokine storm, it is important not to miss a time point of developing immunosuppressive condition that transitions into immunoparalysis as follows from recent publications covering the tactics of treating immune-mediated complications of coronavirus infection. The review discusses opportunities for immunosuppressive therapy along with glucocorticosteroids and monoclonal antibodies blocking IL-6 or cognate receptors. Studies using mesenchymal stem cells (MSCs) to reduce systemic inflammatory response at COVID-19 are outlined in the review. The use of antigen-specific Treg and their combinations with antagonists of tumor necrosis factor- (TNF), interferon- (IFN) as well as low-dose IL-2 in patients with SARS-CoV-2 infection were analyzed. The prognostic perspectives for CAR-T cells and CAR-NK cells technology have been considered as novel therapeutic approaches aimed at training effector cells to recognize the surface SARS-CoV-2 virus spike-like (S) protein. The feasibility of a therapeutic approach is also emphasized by comparatively analyzed of efficacy of using IL-7 or IL-15 during lymphopenia in patients with COVID-19. Here, side effects complicating immunocorrection come to the fore. Critical evaluation of corrected immunosuppressive conditions in patients with COVID-19 in the post-COVID-19 period by using low-dose IL-2 therapy revealed its ability to repair cellular immune response. As a result, a low-dose IL-2 therapy is recommended as a cytokine replacement therapy in such patients with COVID-19 during hyper-to-hypo-inflammatory phase transition in immune response.

Idiopathic Immunodeficiency in Cytomegalovirus Reactivation: A Rare Case

Idiopathic CD4 lymphocytopenia (ICL) is a rare condition characterized by an unexplained deficit of circulating CD4 T cells leading to increased risk of serious opportunistic infections. Reactivation and severe symptomatic CMV is also a rare case, except in immunocompromised patient. Patient concerns are 36-year-old male patient complained seizure, fever, cough, and dyspnea. History of chronic urticaria and prolonged Mebhydrolin consumption. HIV was negative. CD4 was low. Diagnosis in this case is Viral encephalitis, Viral pneumonitis, CMV reactivation, hemophagocytic lymphohistiocytosis immunodeficiency state. The results in this study indicate that the patients were treated with conventional therapies for Severe CMV infection with Acyclovir. Steroid was given for the last five days. The first day after administration of therapy showed clinical and laboratory improvement. Laboratory values returned to normal values on the fifth day of therapy. Since the second day after the therapy was given, the patient had no complaints. In cases of CMV reactivation, an immunodeficiency condition should be suspected. A comprehensive history, physical examination, laboratory and radiological examination, adequate therapy and and policy support are required to establish a definite diagnosis and reduce the risk of mortality.

Hepatitis B virus-induced CD4 lymphocytopenia: A rare cause of progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a rare subacute-onset fatal demyelinating disease of the central nervous system caused by the John Cunningham (JC) virus. It usually occurs in impaired cell-mediated immunity settings such as lymphoproliferative disorders, chronic infective or granulomatous conditions on immunosuppressive medications, and human immunodeficiency virus infection. It also appears very rarely with idiopathic CD4 lymphocytopenia. We present a case of PML with visual field defect, progressive motor impairment, behavioral alteration, and dementia. Magnetic resonance imaging had features of asymmetric non-enhancing hyperintense subcortical white matter lesions in the background of chronic active hepatitis B infection. To the best of our knowledge, this is the first case report of CD4 lymphocytopenia associated PML following chronic hepatitis B infection.

ABCL-385 CD4 Counts and Viral Loads for Screening of HIV-Associated Lymphoma

Lymphoma is a leading cause of death in HIV patients, with up to 400-fold increased incidence compared to HIV-negative individuals. There tends to be a downtrend in CD4 lymphocyte counts noted at the diagnosis of lymphoma in HIV patients, despite virologic control. Some reports have described a preceding downtrend of CD4 counts almost a year prior to lymphoma diagnosis. The pathophysiology of this CD4 decline remains largely unknown, and the implications of this finding on prognosis, infection risk, or response to therapy are unclear. To date, there are no significant interventions suggested in response to this finding. Further characterization of this decline may provide clinical utility for identifying high-risk patients and intervening earlier, both by way of treatment and prophylaxis. We performed a retrospective chart review of patients with HIV-associated lymphoma treated at the UTMB oncology clinic between 2020 to 2021. We identified 3 patients with HIV-associated lymphoma, all notably with diffuse large B-cell lymphoma (DLBCL). We analyzed their CD4 counts and HIV viral loads from the time of diagnosis to 1 year after treatment completion, their rates of infectious complications, and lymphoma treatment outcomes. Hematology and Oncology Clinic Results: All patients had CD4 counts <100 with undetectable HIV on quantitative PCR at lymphoma diagnosis. All received chemo-immunotherapy, predominantly the R-EPOCH regimen, and standard infection prophylaxis according to guidelines. Two patients presented with a significant rise in absolute CD4 levels throughout the treatment course, whereas 1 had minimally rising levels initially that then declined. All patients achieved complete responses to systemic therapy with no infectious complications and no significant relapses. There is a lack of clear explanation for CD4 lymphopenia decline prior to and at the time of HIV-associated lymphoma diagnosis, despite optimal HIV control. Lymphocyte recruitment to lymphomagenesis sites may contribute to the low CD4 count in peripheral blood, which may explain their preceding decline. Screening such patients for lymphoma diagnosis might help with early-stage diagnosis and prognosis improvement. Large-scale studies are needed to better evaluate the implications of our findings and make potential changes to the management algorithm of HIV-associated lymphoma.

Increased percentage of apoptotic and CTLA-4 (CD152) expressing cells in CD4+/CD8+ cells in COVID-19 patients.

Coronavirus infectious disease 2019 (COVID-19) confirmed cases are characterized by T lymphopenia. Total apoptotic and cytotoxic T-lymphocyte antigen-4 (CTLA-4) expressing cells among CD4+/CD8+ cells were analyzed in 24 COVID-19 patients (16 out-patients and 8 in-patients) and 18 healthy volunteers using flow cytometry to detect their possible role in T lymphopenia. Hospitalized patients did not show significant difference compared to non-hospitalized patients. While the percentage and absolute count of CD4+/CD8+ cells were significantly reduced in COVID-19 cases compared to healthy control (P < .05), the proportion of apoptotic and CTLA-4 expressing CD4+/CD8+ cells were significantly up-regulated in COVID-19 patients (P < .05). In addition, apoptotic and CTLA-4+/CD4+ cells were directly related to dyspnea duration, chest CT score, ferritin, and C-reactive protein and inversely correlated with platelet count in COVID-19 patients. While apoptotic and CTLA-4+/CD8+ cells were directly related to lymphocyte count in COVID-19 patients. The apoptotic and CTLA-4+ cells were directly related to each other in CD4+/CD8+ cells (P < .05). White blood cells (WBCs) (×103/L), eosinophils (ratio and count), lymphocyte ratio, neutrophil ratio, neutrophil/lymphocyte ratio, neutrophil/CD4 ratio, neutrophil/CD8 ratio, CD4+ cells ratio, and CTLA-4+ cells percentage), and CD8+ cells (ratio, count, total apoptotic cell, and CD152 + cells) were all found to be significantly altered in association with COVID-19. Total lymphopenia and depletion of CD4+/CD8+ cells are characterizing COVID-19 patients. Increased apoptosis and CTLA-4 expression in CD4+/CD8+ cells in COVID-19 and their correlations with reduced cell count and severity indicators as CRP and ferritin can be used for diagnosis and follow up of the clinical severity. Our current study proposes promising future diagnostic and therapeutic targets.

34244 Acquired epidermodysplasia verruciformis: A retrospective review of cases

Epidermodysplasia verruciformis is a rare genodermatosis characterized by an unusual susceptibility to the beta genus of the human papillomavirus and early development of skin cancers. Acquired epidermodysplasia verruciformis (AEDV) is a distinct rare disorder with similar clinical and histopathologic manifestation, strongly associated with immunosuppression. Clinical course, therapeutic management, and potential for skin cancer development in AEDV is largely unknown. We report 7 patients with AEDV diagnosed between January 1992 and November 2019. Four patients were males (57.1%), with median age of diagnosis of 29 years, range 9-67 years. All patients had underlying immunodeficiency; 5 with acquired immunodeficiencies (HIV/AIDS, heart transplant, kidney transplant, pancreas transplant, systemic lupus erythematosus and Crohn’s disease) and 2 with congenital immunodeficiencies (isolated CD4 lymphopenia and immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia). For patients with acquired immunodeficiencies, the median interval between the onset of immunosuppression and the presentation of AEDV lesions was 5 years, range 3-7 years. Patients were followed for a median of 5.5 years, range 1-10 years. Only 1 patient (14.2%) progressed to develop squamous cell carcinoma of the left forearm. Topical imiquimod (3/7), topical tretinoin (3/7), cryotherapy (2/7), intralesional candida injection (2/7), and topical podophyllotoxin (1/7) were attempted for treatment of AEDV. Partial resolution of AEDV lesions was observed with intralesional candida injection (2/2) and topical retinoid (1/3). Initiation of HAART yielded complete resolution in one patient with HIV/AIDS. In conclusion, we report a series of AEDV with emphasis on therapeutic management, clinical course, and long-term follow up of this rare disorder.

Laryngeal Histoplasmosis in an Immunocompromised Host

Laryngeal histoplasmosis is a rare manifestation of histoplasmosis infection and presents as a diagnostic challenge. It has been documented to occur in immunocompromised and immunocompetent hosts. This is a case of laryngeal histoplasmosis in a patient with idiopathic CD4 lymphocytopenia, an immunocompromising condition that presents similarly to HIV. There is no known cause or standardized treatment of idiopathic CD4 lymphocytopenia, which leaves patients at risk for opportunistic infections and malignancy.

Des bleus mais pas de coups

AbstractA 2-month-old newborn was hospitalized for hemorrhagic picture associated with deterioration of his general condition and eczema. A thrombocytopenia is highlighted, without any other alteration of coagulation. As the patient develops pneumocystis jirovecii infection and signs of vasculitis, immune deficiency is suspected. The discovery of CD8 lymphopenia, microthrombocytopenia, and the presence of eczema, lead to a diagnosis of Wiskott-Aldrich syndrome, then confirmed by molecular biology.

Neonate with Respiratory Distress, Bilateral Microtia, Hypocalcemia, and Lymphopenia.

Neonate with Respiratory Distress, Bilateral Microtia, Hypocalcemia, and Lymphopenia.

CD4 T cell deficiency results in impaired neutralizing IgG against polyomavirus carrying a frequent PML-associated capsid mutation

Abstract Deficiencies in the CD4 T cell compartment, such as HIV/AIDS, idiopathic CD4 lymphopenia, predispose patients to progressive multifocal leukoencephalopathy (PML), an oft-fatal demyelinating brain disease caused by the JC polyomavirus (JCPyV). PML is associated with immunomodulatory therapies that preferentially diminish CD4 T cells in the CSF (natalizumab) or B cells (rituximab). The connection between CD4 T cells and JCPyV control is unclear. Work by others show that PML patient sera have “blind spots” in neutralizing JCPyV variants with mutations in the VP1 capsid protein. We hypothesized that defects in the humoral response after CD4 T cell depletion led to the emergence of antibody (Ab)-escape PyV variants. Using mouse PyV (MuPyV) to model JCPyV CNS disease, we found immune cell aggregates consisting of B cells, CD4 T cells, and CD8 T cells along the ventricles of PyV-infected WT mice but only a few infected cells. In contrast, CD4 T cell-depleted mice had more infected ependyma but lacked lymphocytic aggregates. There were fewer anti-PyV Ab-secreting B cells in the CNS despite similar B cell numbers in MuPyV-infected WT and CD4 T cell deficient mice brains. CD4 T cells prevent emergence of VP1 mutant PyVs that escape neutralizing Abs. MuPyV infection elicits a CD4 T cell-independent anti-VP1 IgG response that neutralizes WT virus equivalently to IgG from CD4 T cell-sufficient mice. Serum from MHC-II KO and CD4 mAb depleted mice had significantly lower neutralization activity toward a MuPyV with a frequent PML-equivalent VP1 mutation than to WT MuPyV. This data demonstrate that a narrowed antiviral IgG response caused by CD4 T cell deficiency is a critical antecedent for outgrowth of Ab-escape PyV VP1 mutant viruses. Supported by 1. Finkelstein Memorial Student Research Award, Pennsylvania State University College of Medicine, Hershey, PA 2. T32 CA060395 Training Grant (Meyers), NIH/NCI 3. R01 NS088367, NIH/NCI

EBV-POSITIVE B-CELL ULCERATIVE PROLIFERATION IN THE ORAL CAVITY

<h3>Objective</h3> Lymphoproliferative disorders (LPDs) are a group of conditions characterized by excessive production of lymphocytes manifested by lymphadenopathy, monoclonal lymphocytosis, and bone marrow infiltration. LPDs are often associated with Epstein-Barr virus (EBV) infection. EBV-associated LPDs most commonly appear in the setting of immunocompromised status such as HIV and in transplantation with the extended use of immunosuppressive medications. Individuals with primary immunodeficiency disorders, such as common variable immunodeficiency disease (CVID) or severe combined immunodeficiency, are also at risk of LPD. <h3>Case Summary</h3> A 67-year-old woman complained of mouth ulcerations for 3 months before presentation that were progressively getting worse. Past medical history included CVID, CD4 lymphopenia, rhinosinusitis, eosinophilic asthma, chronic back pain, anxiety, and depression. Medications included immunoglobulin replacement therapy, mepolizumab, montelukast, albuterol, cetirizine, bupropion, clonazepam, fluoxetine, and gabapentin. The patient was allergic to penicillin and azithromycin. Past surgical history was notable for removal of skin melanoma and total knee replacement. Review of systems included a 3-month, 25-lb weight loss, odynophagia, constipation, weakness, and fatigue. Extraoral examination was unremarkable. Intraoral examination revealed 3 × 2 cm² necrotizing palatal ulcerations bilaterally. Necrotizing ulceration was also noted on multiple areas of the gingiva. Differential diagnosis included acute necrotizing ulcerative periodontitis, deep fungal infection (aspergillosis), and lymphoma/LPD. Complete blood count with differential, EBV polymerase chain reaction (PCR), cytomegalovirus PCR and maxillofacial computed tomography (CT) were ordered. The CT scan was unremarkable and laboratory evaluation was negative except for positive EBV PCR. Oral biopsy demonstrated EBV positive B-cell ulcerative proliferation. Positron emission tomography/CT showed widespread fluorodeoxyglucose (FDG)-avid lymphadenopathy. An axillary lymph node biopsy showed atypical lymphoid proliferation in a background of atypical and reactive follicular hyperplasia most consistent with EBV-negative follicular lymphoma, which appeared histologically distinct from the oral EBV-positive LPD. The patient is currently being treated with single-agent rituximab therapy. <h3>Conclusions</h3> EBV may cause oral diseases including infectious mononucleosis, oral hairy leukoplakia, necrotizing ulcerative mucositis, non-Hodgkin's lymphoma, and EBV-related LPD. Persistent oral lesions in patients with CVID could be related to underlying systemic disease. This case is unique because the patient seemingly had follicular lymphoma unrelated to her EBV-positive LPD oral disease, yet in the setting of severe immunosuppression from CVID.

Identification of a novel MAGT1 mutation supports a diagnosis of XMEN disease

XMEN (X-linked immunodeficiency with magnesium defect) is caused by loss-of-function mutations in MAGT1 which is encoded on the X chromosome. The disorder is characterised by CD4 lymphopenia, severe chronic viral infections and defective T-lymphocyte activation. XMEN patients are susceptible to Epstein-Barr virus infections and persistently low levels of intracellular Mg2+. Here we describe a patient that presented with multiple recurrent infections and a subsequent diffuse B-cell lymphoma. Molecular genetic analysis by exome sequencing identified a novel hemizygous MAGT1 nonsense mutation c.1005T>A (NM_032121.5) p.(Cys335*), confirming a diagnosis of XMEN deficiency. Follow-up immunophenotyping was performed by antibody staining and flow cytometry; proliferation was determined by 3H-thymidine uptake after activation by PHA and anti-CD3. Cytotoxic natural killer cell activity was assessed with K562 target cells using the NKTESTTM assay. While lymphocyte populations were superficially intact, B cells were largely naive with a reduced memory cell compartment. Translated NKG2D was absent on both NK and T cells in the proband, and normally expressed in the carrier mother. In vitro NK cell activity was intact in both the proband and his mother. This report adds to the growing number of identified XMEN cases, raising awareness of a, still rare, X-linked immunodeficiency.

New onset of autoimmune diseases in patients with primary antibody deficiency and CD4 lymphopenia after COVID-19

Patients with primary antibody deficiency (PAD) have increased susceptibility to infectious and non-infectious complications including autoimmune diseases. It is speculated that SARS-CoV-2 can disturb self-tolerance and trigger autoimmune responses in COVID-19. Here, we present two cases of patients with PAD who developed new onset of autoimmune disease after COVID-19.