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Gene & Protein in Disease Monogenic lupus and interferonopathies

Table 2. Clinical and laboratory features and treatment
regimens for patients with monogenic lupus
Patient 1 Patient 2
Gender Male Female
Age at onset 3 years 7 years
Age at diagnosis 12 years 12 years
Clinical features
Constitiutional Fever, fatigability, Fever, fatigability,
weight loss weight loss
Figure 3. The distinction between monogenic lupus variants associated
Mucocutaneous No Facial rash, oral ulcers, with interferonopathy (autoinflammatory features) and those involving
periorbital swelling B-cell/T-cell dysfunction (autoimmune features)
Musculoskeletal Painful polyarthritis Polyarthritis, proximal
muscle weakness interplay between IFN-I, Th17 cells, and sHLA-G into
Neuropsychiatric Headache, Seizure, behavioral, the understanding of monogenic lupus may help clarify
papilledema learning disability the diverse and overlapping immunopathogenic features
Renal No No observed in these cases.
Lung No No At present, there are no approved medications
Cardiac No No specifically for patients with monogenic lupus or
Gastrointestinal No No interferonopathies. However, available medications,
Recurrent infection No No including biologic agents, are used off-label. Our
Laboratory features patients were successfully treated with corticosteroids,
ANA 1:1280 1:1280 hydroxychloroquine, mycophenolate mofetil, and
dsDNA 1294 770 belimumab. Emerging treatment modalities, such as
Hematologic Leukopenia, DC Anemia Janus Kinase inhibitors (e.g., tofacitinib, baricitinib,
positive anemia or ruxolitinib), interferon receptor blockade (e.g.,
Acute-phase High ESR, CRP High ESR, CRP anifrolumab), or agents targeting free phases of type I
reactants interferons (e.g., sifalimumab or rontalizumab), show
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Serum High Normal promise for treating interferonopathies. Notably, the
immunoglobluins recent approval of anifrolumab, in addition to belimumab,
Brain imaging Multiple scattered Bilateral diffuse has expanded treatment options for lupus in general. 29-31
(MRI) hyperintense lesions T2 hyperintensities in the This report highlights the growing recognition of
in the bilateral temporal lobes shared immunopathogenic pathways between monogenic
cerebral white matter
Treatment HCQ, MMF, HCQ, MMF, belimumab lupus and autoinflammatory disorders, particularly in the
belimumab context of type I interferon-mediated disease. Monogenic
Present status Stable general Stable general condition, lupus exhibits significant variability due to diverse
condition, persistent behavioral, and learning immune system etiopathogenesis. The interferon pathway,
deforming arthropathy disability which connects autoimmunity and autoinflammation
Abbreviations: ANA: Antinuclear antibody; CRP: C-reactive protein; by linking innate and adaptive immune responses, is
DC: D-Coombs; dsDNA: double-stranded DNA; ESR: Erythrocyte associated with a range of genetic variants responsible for
sedimentation rate; HCQ: Hydroxychloroquine; MMF: Mycophenolate monogenic lupus. However, considering monogenic lupus
mofetil; MRI: Magnetic resonance imaging. under autoinflammatory classification may not be ideal,
given lupus’s historical classification as an autoimmune
polarization under interferon-driven environments. disease. Therefore, we propose adopting the concept of
Moreover, sHLA-G, an immunomodulatory molecule, monogenic interferonopathies as a stand-alone category.
has been reported to impact both innate and adaptive This category would encompass a broad spectrum of
immunity, potentially modulating the balance between conditions, including monogenic autoinflammatory,
regulatory and pro-inflammatory responses. These monogenic lupus, as they bridge autoimmune and
interactions are thought to drive persistent inflammation autoinflammatory disorders. However, a consensus is
and autoimmunity, as highlighted in recent studies by required to formulate the monogenic interferonopathies
Murdaca et al. and Contini et al. Incorporating the taxonomy and nomenclature.
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Volume 4 Issue 3 (2025) 4 doi: 10.36922/GPD025080019